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First published online November 7, 2007
doi: 10.1242/10.1242/jcs.015909
Cell Science at a Glance |
1 Department of Pathology MSC08-4640, University of New Mexico, 2325 Camino de Salud NE, CRF225, Albuquerque, NM 87131, USA
2 Departments of Structural Biology and Physical Biochemistry, Max Planck Institute for Molecular Physiology, 44227 Dortmund, Germany
3 Sanofi-Aventis, Centre de Recherche Paris, 13, Quai Jules Guesde–BP 14, 94403 Vitry sur Seine Cedex, France
* Author for correspondence (e-mail: wness{at}unm.edu)
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Introduction |
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 Top Introduction Rab GTPases regulate membrane...Rab proteins temporally and...The Rab family treeRab proteins as scaffoldsRab proteins in disease...References |
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; Schmitt et al., 1986; Touchot et al., 1987). The proteins are members of the wider Ras superfamily of GTPases (Wennerberg et al., 2005). Over 70 human Rab and Rab-like members of the Ras superfamily have been identified (Colicelli, 2004; Stenmark and Olkkonen, 2001), and the functions of 36 Rab GTPases have been delineated. Rab GTPases are molecular switches, cycling between active and inactive states and serving as scaffolds to integrate both membrane trafficking and intracellular signaling in a temporally and spatially sensitive manner (Bucci and Chiariello, 2006; Zerial and McBride, 2001). Despite the small sizes of Rab proteins (20-25 kDa), structural analyses reveal they have multiple interaction surfaces through which they associate with regulatory molecules and downstream effectors to exert their functions (Chen et al., 2003; Pereira-Leal and Seabra, 2000; Pfeffer, 2005).
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Rab GTPases regulate membrane trafficking, cell growth and differentiation |
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TopIntroductionRab GTPases regulate membrane...Rab proteins temporally and...The Rab family treeRab proteins as scaffoldsRab proteins in disease...References |
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Rab proteins are best known for their essential roles in exocytic and endocytic membrane trafficking, which encompass the constitutive and regulated secretory routes, endocytosis via caveolae or clathrin-coated vesicles (CCVs), micropinocytosis and phagocytosis. They control anterograde and retrograde trafficking between compartments to coordinate cargo delivery and membrane recycling and also subcompartmentalize organelles by organizing specific membrane domains that function in trafficking of cargo to different destinations (colored lines on the poster denote such domains; the micrograph illustrates alternating Rab7 and Rab5 domains on dilated early endosomes) (Barbero et al., 2002; Vitale et al., 1998; Vonderheit and Helenius, 2005). In this way, Rab GTPases regulate plasma membrane delivery, organelle biogenesis and degradative pathways (lysosomal and autophagic). They also contribute to cell-type-specific functions, such as regulated secretion (secretory granules/lysosomes in endocrine and exocrine cells), synaptic transmission [synaptic vesicles (SVs) in neurons] and phagocytosis (in macrophages and dendritic cells). In epithelia, Rab GTPases help generate polarity by regulating the trafficking of junctional proteins and integrins and by defining epithelial transport circuits to cilia (connecting with intraflagellar transport, IFT), the apical (AM) and basolateral (BM) membranes, and apical recycling endosomes (AREs). They thus play major regulatory roles maintaining compartment identity, regulating cargo delivery, controlling protein and lipid storage/degradation and modulating specialized trafficking functions.
Rab proteins are increasingly found downstream of signaling cascades and can impact gene expression and growth control. Rab5, for example, is implicated in EGF signaling and thought to sequester APPL1, an adaptor protein involved in chromatin remodeling, apoptosis and gene expression, on endosomes so it cannot enter the nucleus until activation signals are received (Bucci and Chiariello, 2006; Miaczynska et al., 2004). Rab family members that signal to the nucleus (Rab5, Rab8, Rab24 and possibly others) might work in concert with the Ran GTPase (also a Rab family member), which controls nucleocytoplasmic shuttling, to bring about rapid responses to signaling that require changes in cell growth or differentiation (Joseph, 2006; Miaczynska et al., 2004; Wu et al., 2006). Rab32, which regulates mitochondrial fission, may participate in adaptation to changing energy requirements during growth (Alto et al., 2002; Hood et al., 2006). Cell growth and differentiation may in turn be modulated through the coordinated actions of Rab GTPases regulating cell-matrix and cell-cell adhesion (Rab4a, Rab8b, Rab13 and Rab21) and those involved in growth-regulatory signaling and mitosis or apoptosis (Rab6a', Rab11, Rab12, Rab23, Rab25, Rab35, Ran and likely others) (Bucci and Chiariello, 2006; Del Nery et al., 2006; Fan et al., 2006; Iida et al., 2005; Kouranti et al., 2006; Wang et al., 2006; Yu et al., 2007).
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Rab proteins temporally and spatially control vesicular transport |
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TopIntroductionRab GTPases regulate membrane...Rab proteins temporally and...The Rab family treeRab proteins as scaffoldsRab proteins in disease...References |
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; Stenmark and Olkkonen, 2001; Zerial and McBride, 2001). They sequentially interact with specific effectors to facilitate vesicular transport from vesicle budding to fusion. In addition, interfaces with intracellular signaling cascades can serve to up- or downregulate transport, depending on cellular requirements.
The membrane association/dissociation and nucleotide binding/hydrolysis cycles are intimately connected and regulated by specific chaperones. Rab family members are modified by a prenyl moiety at their C-termini (Rab44, Rab-like proteins and Ran are notable exceptions) (Colicelli, 2004; Leung et al., 2006; Leung et al., 2007). The increased hydrophobicity due to prenylation necessitates delivery to the appropriate membrane by accessory factors such as Rab escort protein (REP) after synthesis (Goody et al., 2005). Once delivered to the membrane, Rab proteins are activated by the exchange of GDP for GTP, triggered by guanine nucleotide exchange factors (GEFs). Once an individual transport step is completed, GTPase-activating proteins (GAPs) accelerate Rab GTP hydrolysis allowing recognition by a GDP dissociation inhibitor (GDI), which sequesters the Rab in the cytosol until it is recruited to a membrane and begins the transport cycle again (Goody et al., 2005).
Regulation of Rab activation and inactivation may be linked to signaling in order to allow dynamic responsiveness to cellular trafficking needs. Rab regulatory proteins (GEFs, GAPs and GDIs) are phosphorylated in response to stress and growth factor signaling, thereby enhancing or diminishing Rab activity and resulting in up- or downregulation of constitutive and regulated trafficking (Bucci and Chiariello, 2006; Roach et al., 2007). For example, in insulin signaling, phosphorylation of the Rab GAPs Tbc1d4/AS160 and Tbc1d1 by Akt (protein kinase B) results in heightened levels of activated Rab proteins involved in trafficking and fusion of glucose transporter (Glut4) vesicles with the plasma membrane.
Activated Rab proteins serve as molecular scaffolds to coordinate three main membrane-trafficking steps: vesicle budding, cytoskeletal transport, and targeted docking and fusion (Grosshans et al., 2006; Stein et al., 2003). Consequently, Rab proteins interact sequentially with many downstream effector proteins in a temporally and spatially regulated manner. To induce vesicle budding, Rab proteins promote cargo selection. Rab9, for example, binds to tail-interacting protein 47 kDa (TIP47), which mediates Golgi recyling of the mannose 6-phosphate receptor from endosomes (Carroll et al., 2001). Rab GTPases also cooperate with Arf GTPases to recruit vesicle coats. Rab11, for example, may regulate protein coat recruitment via ARF4 and the Arf GAP ASAP1 and enable rhodopsin transport from the TGN to the rod outer segment of photoreceptor cells (Deretic, 2006). Following budding, a number of Rab proteins (e.g. Rab6, Rab7, Rab11 and Rab27) are known to recruit actin- or microtubule-based motor protein complexes (MPCs) that transport vesicles along cytoskeletal filaments (Jordens et al., 2005). Finally, Rab proteins help recruit tethering factors, which help target the carrier to the appropriate membrane, as well as SNARES, which may directly promote homotypic or heterotypic membrane fusion (Grosshans et al., 2006; Markgraf et al., 2007). On the endocytic pathway, Rab proteins also scaffold lipid kinases and phosphatases to control budding and fusion (the micrograph illustrates colocalization of the myotubularin phosphatase MTM1, the lipid kinase hVPS34 and Rab7) (Cao et al., 2007; Shin et al., 2005).
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The Rab family tree |
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TopIntroductionRab GTPases regulate membrane...Rab proteins temporally and...The Rab family treeRab proteins as scaffoldsRab proteins in disease...References |
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; Stenmark and Olkkonen, 2001). Further isoform diversity is generated through ongoing mRNA processing in the form of alternative splicing (Dou et al., 2005). Ran, a GTPase initially thought to define a separate family, and several recently identified Rab-like GTPases are categorized as part of the Rab family on the basis of comparative sequence analyses (Colicelli, 2004). Dendrogram clustering suggests 14 Rab subfamilies (Table 1). One must exercise caution, however, in making structure/function predictions about uncharacterized members (denoted in red in Table 1) on the basis of these sequence-derived clusters. For any given subfamily the alignments do not differentiate whether the sequence similarity underlies a common basic structure, effector binding, regulatory protein interactions, subcellular localization or another aspect of the protein. Many Rab isoforms bind different effectors and have unique subcellular localizations. Hence, one must consider a number of other factors when extrapolating Rab functions.
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Rab proteins as scaffolds |
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TopIntroductionRab GTPases regulate membrane...Rab proteins temporally and...The Rab family treeRab proteins as scaffoldsRab proteins in disease...References |
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). The Rab7 structure has also been solved in a complex with a regulatory protein (REP1) and an effector (RILP) and therefore serves as an instructive example (Rak et al., 2004; Wu et al., 2005). The GDP- and GTP-bound forms of Rab7 demonstrate the significant conformational changes in the Switch I (blue) and II (pink) regions that occur as a consequence of GTP binding and hydrolysis (Goody et al., 2005; Pereira-Leal and Seabra, 2000). So far, comparison of Rab7 in complexes with RILP and REP1 reveals two overlapping surfaces that are important for protein-protein interactions. At least two disease-causing mutations, outside the nucleotide-binding pocket of Rab7, disrupt effector interactions (Mukherjee and Wandinger-Ness unpublished observations), which suggests that additional protein-interaction surfaces exist. Rab7 and other Rab proteins have discrete protein-protein interaction surfaces that enable them to play pivotal roles as molecular scaffolds. Structural overlays of Rab GTPases and analyses of protein-protein interaction surfaces will be crucial if we are to understand how Rab GTPases and their effectors function and contribute to human disease when mutated (Pfeffer, 2005; Stein et al., 2003). |
Rab proteins in disease and as drug targets |
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TopIntroductionRab GTPases regulate membrane...Rab proteins temporally and...The Rab family treeRab proteins as scaffoldsRab proteins in disease...References |
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; Chua and Tang, 2006; Di Pietro and Dell'Angelica, 2005; Inglis et al., 2006). Thus, the Rab GTPases are prime drug targets, prompting our group and others to undertake high-throughput screens. The wealth of functional assays and structural data are expected to enable discrimination of specific and effective compounds in the near future. |
Acknowledgments |
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Footnotes |
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A link between Ran and apicobasal polarity and ciliogenesis has recently been established suggesting the interconnections between Rab-regulated membrane transport and nuclear signaling will be an important area for further study (Fan S. et al., 2007).
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References |
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|
TopIntroductionRab GTPases regulate membrane...Rab proteins temporally and...The Rab family treeRab proteins as scaffoldsRab proteins in disease...References |
|---|
Allan, B. B., Moyer, B. D. and Balch, W. E. (2000). Rab1 recruitment of p115 into a cis-SNARE complex: programming budding COPII vesicles for fusion. Science 289, 444-448.
Alto, N. M., Soderling, J. and Scott, J. D. (2002). Rab32 is an A-kinase anchoring protein and participates in mitochondrial dynamics. J. Cell Biol. 158, 659-668.
Arnett, A. L., Bayazitov, I., Blaabjerg, M., Fang, L., Zimmer, J. and Baskys, A. (2004). Antisense oligonucleotide against GTPase Rab5b inhibits metabotropic agonist DHPG-induced neuroprotection. Brain Res. 1028, 59-65.[CrossRef][Medline]
Babbey, C. M., Ahktar, N., Wang, E., Chen, C. C., Grant, B. D. and Dunn, K. W. (2006). Rab10 regulates membrane transport through early endosomes of polarized Madin-Darby canine kidney cells. Mol. Biol. Cell 17, 3156-3175.
Barbero, P., Bittova, L. and Pfeffer, S. R. (2002). Visualization of Rab9-mediated vesicle transport from endosomes to the trans-Golgi in living cells. J. Cell Biol. 156, 511-518.
Barbieri, M. A., Roberts, R. L., Gumusboga, A., Highfield, H., Alvarez-Dominguez, C., Wells, A. and Stahl, P. D. (2000). Epidermal growth factor and membrane trafficking. EGF receptor activation of endocytosis requires Rab5a. J. Cell Biol. 151, 539-550.
Barral, D. C., Ramalho, J. S., Anders, R., Hume, A. N., Knapton, H. J., Tolmachova, T., Collinson, L. M., Goulding, D., Authi, K. S. and Seabra, M. C. (2002). Functional redundancy of Rab27 proteins and the pathogenesis of Griscelli syndrome. J. Clin. Invest. 110, 247-257.[CrossRef][Medline]
Bottger, G., Nagelkerken, B. and van der Sluijs, P. (1996). Rab4 and Rab7 define distinct nonoverlapping endosomal compartments. J. Biol. Chem. 271, 29191-29197.
Brachvogel, V., Neu, M. and Metcalf, P. (1997). Rab7: crystallization of intact and C-terminal truncated constructs complexed with GDP and GppNHp. Proteins 27, 210-212.[CrossRef][Medline]
Brunner, Y., Coute, Y., Iezzi, M., Foti, M., Fukuda, M., Hochstrasser, D., Wollheim, C. and Sanchez, J. C. (2007). Proteomic analysis of insulin secretory granules. Mol. Cell. Proteomics 6, 1007-1017.
Bucci, C. and Chiariello, M. (2006). Signal transduction gRABs attention. Cell. Signal. 18, 1-8.[CrossRef][Medline]
Bucci, C., Lutcke, A., Steele-Mortimer, O., Olkkonen, V. M., Dupree, P., Chiariello, M., Bruni, C. B., Simons, K. and Zerial, M. (1995). Co-operative regulation of endocytosis by three Rab5 isoforms. FEBS Lett. 366, 65-71.[CrossRef][Medline]
Bucci, C., Thomsen, P., Nicoziani, P., McCarthy, J. and van Deurs, B. (2000). Rab7: a key to lysosome biogenesis. Mol. Biol. Cell 11, 467-480.
Cao, C., Laporte, J., Backer, J. M., Wandinger-Ness, A. and Stein, M.-P. (2007). Myotubularin lipid phosphatase binds the hVPS15/hVPS34 lipid kinase complex on endosomes. Traffic 8, 1052-1067.[CrossRef][Medline]
Carroll, K. S., Hanna, J., Simon, I., Krise, J., Barbero, P. and Pfeffer, S. R. (2001). Role of Rab9 GTPase in facilitating receptor recruitment by TIP47. Science 292, 1373-1376.
Casanova, J. E., Wang, X., Kumar, R., Bhartur, S. G., Navarre, J., Woodrum, J. E., Altschuler, Y., Ray, G. S. and Goldenring, J. R. (1999). Association of Rab25 and Rab11a with the apical recycling system of polarized Madin-Darby canine kidney cells. Mol. Biol. Cell 10, 47-61.
Chen, J., Anderson, J. B., DeWeese-Scott, C., Fedorova, N. D., Geer, L. Y., He, S., Hurwitz, D. I., Jackson, J. D., Jacobs, A. R., Lanczycki, C. J. et al. (2003). MMDB: Entrez's 3D-structure database. Nucleic Acids Res. 31, 474-477.
Chen, S., Liang, M. C., Chia, J. N., Ngsee, J. K. and Ting, A. E. (2001). Rab8b and its interacting partner TRIP8b are involved in regulated secretion in AtT20 cells. J. Biol. Chem. 276, 13209-13216.
Chen, W. and Wandinger-Ness, A. (2001). Expression and functional analyses of Rab8 and Rab11a in exocytic transport from trans-Golgi network. Meth. Enzymol. 329, 165-175.[Medline]
Chen, Y. T., Holcomb, C. and Moore, H. P. (1993). Expression and localization of two low molecular weight GTP-binding proteins, Rab8 and Rab10, by epitope tag. Proc. Natl. Acad. Sci. USA 90, 6508-6512.
Cheng, K. W., Lahad, J. P., Gray, J. W. and Mills, G. B. (2005). Emerging role of RAB GTPases in cancer and human disease. Cancer Res. 65, 2516-2519.
Chua, C. E. and Tang, B. L. (2006). alpha-synuclein and Parkinson's disease: the first roadblock. J. Cell. Mol. Med. 10, 837-846.[Medline]
Colicelli, J. (2004). Human RAS superfamily proteins and related GTPases. Sci. STKE 2004, RE13.[CrossRef][Medline]
Colucci, A. M., Spinosa, M. R. and Bucci, C. (2005). Expression, assay, and functional properties of RILP. Meth. Enzymol. 403, 664-675.[Medline]
Curtis, L. M. and Gluck, S. (2005). Distribution of Rab GTPases in mouse kidney and comparison with vacuolar H+-ATPase. Nephron Physiol. 100, p31-p42.[CrossRef][Medline]
Del Nery, E., Miserey-Lenkei, S., Falguieres, T., Nizak, C., Johannes, L., Perez, F. and Goud, B. (2006). Rab6A and Rab6A' GTPases play non-overlapping roles in membrane trafficking. Traffic 7, 394-407.[CrossRef][Medline]
Deretic, D. (2006). A role for rhodopsin in a signal transduction cascade that regulates membrane trafficking and photoreceptor polarity. Vision Res. 46, 4427-4433.[CrossRef][Medline]
Di Pietro, S. M. and Dell'Angelica, E. C. (2005). The cell biology of Hermansky-Pudlak syndrome: recent advances. Traffic 6, 525-533.[CrossRef][Medline]
Dou, T., Ji, C., Gu, S., Chen, F., Xu, J., Ye, X., Ying, K., Xie, Y. and Mao, Y. (2005). Cloning and characterization of a novel splice variant of human Rab18 gene (RAB18)dagger. DNA Seq. 16, 230-234.[Medline]
Elferink, L. A. and Strick, D. J. (2005). Functional properties of rab15 effector protein in endocytic recycling. Meth. Enzymol. 403, 732-743.[Medline]
Evans, T. M., Ferguson, C., Wainwright, B. J., Parton, R. G. and Wicking, C. (2003). Rab23, a negative regulator of hedgehog signaling, localizes to the plasma membrane and the endocytic pathway. Traffic 4, 869-884.[CrossRef][Medline]
Fan, Y., Xin, X. Y., Chen, B. L. and Ma, X. (2006). Knockdown of RAB25 expression by RNAi inhibits growth of human epithelial ovarian cancer cells in vitro and in vivo. Pathology 38, 561-567.[CrossRef][Medline]
Fan, S., Fogg, V., Wang, Q., Chen, X. W., Liu, C. J. and Margolis, B. (2007). A novel Crumbs3 isoform regulates cell division and ciliogenesis via importin beta interactions. J. Cell Biol. 178, 387-398.
Feng, Y., Press, B., Chen, W., Zimmerman, J. and Wandinger-Ness, A. (2001). Expression and properties of Rab7 in endosome function. Meth. Enzymol. 329, 175-187.[CrossRef][Medline]
Futter, C. E. (2006). The molecular regulation of organelle transport in mammalian retinal pigment epithelial cells. Pigment Cell Res. 19, 104-111.[CrossRef][Medline]
Ganley, I. G., Carroll, K., Bittova, L. and Pfeffer, S. (2004). Rab9 GTPase regulates late endosome size and requires effector interaction for its stability. Mol. Biol. Cell 15, 5420-5430.
Goody, R. S., Rak, A. and Alexandrov, K. (2005). The structural and mechanistic basis for recycling of Rab proteins between membrane compartments. Cell. Mol. Life Sci. 62, 1657-1670.[CrossRef][Medline]
Grosshans, B. L., Ortiz, D. and Novick, P. (2006). Rabs and their effectors: achieving specificity in membrane traffic. Proc. Natl. Acad. Sci. USA 103, 11821-11827.
Hattula, K., Furuhjelm, J., Tikkanen, J., Tanhuanpaa, K., Laakkonen, P. and Peranen, J. (2006). Characterization of the Rab8-specific membrane traffic route linked to protrusion formation. J. Cell Sci. 119, 4866-4877.
Hood, D. A., Irrcher, I., Ljubicic, V. and Joseph, A. M. (2006). Coordination of metabolic plasticity in skeletal muscle. J. Exp. Biol. 209, 2265-2275.
Iida, H., Noda, M., Kaneko, T., Doiguchi, M. and Mori, T. (2005). Identification of rab12 as a vesicle-associated small GTPase highly expressed in Sertoli cells of rat testis. Mol. Reprod. Dev. 71, 178-185.[CrossRef][Medline]
Inglis, P. N., Boroevich, K. A. and Leroux, M. R. (2006). Piecing together a ciliome. Trends Genet. 22, 491-500.[CrossRef][Medline]
Jiang, S. and Storrie, B. (2005). Cisternal rab proteins regulate Golgi apparatus redistribution in response to hypotonic stress. Mol. Biol. Cell 16, 2586-2596.
Jordens, I., Marsman, M., Kuijl, C. and Neefjes, J. (2005). Rab proteins, connecting transport and vesicle fusion. Traffic 6, 1070-1077.[CrossRef][Medline]
Joseph, J. (2006). Ran at a glance. J. Cell Sci. 119, 3481-3484.
Junutula, J. R., De Maziere, A. M., Peden, A. A., Ervin, K. E., Advani, R. J., van Dijk, S. M., Klumperman, J. and Scheller, R. H. (2004). Rab14 is involved in membrane trafficking between the Golgi complex and endosomes. Mol. Biol. Cell 15, 2218-2229.
Kauppi, M., Simonsen, A., Bremnes, B., Vieira, A., Callaghan, J., Stenmark, H. and Olkkonen, V. M. (2002). The small GTPase Rab22 interacts with EEA1 and controls endosomal membrane trafficking. J. Cell Sci. 115, 899-911.
Khvochev, M. V., Ren. M., Takamori, S., Jahn, R. and Sudhof, T. C. (2003). Divergent functions of neuronal Rab11b in Ca2+ regulated versus constituative exocytosis. J. Neurosci. 23, 10531-10539.
Kouranti, I., Sachse, M., Arouche, N., Goud, B. and Echard, A. (2006). Rab35 regulates an endocytic recycling pathway essential for the terminal steps of cytokinesis. Curr. Biol. 16, 1719-1725.[CrossRef][Medline]
Leung, K. F., Baron, R. and Seabra, M. C. (2006). Thematic review series: lipid posttranslational modifications. geranylgeranylation of Rab GTPases. J. Lipid Res. 47, 467-475.
Leung, K. F., Baron, R., Ali, B. R., Magee, A. I. and Seabra, M. C. (2007). Rab GTPases containing a CAAX motif are processed post-geranylgeranylation by proteolysis and methylation. J. Biol. Chem. 282, 1487-1497.
Linder, M. D., Uronen, R. L., Holtta-Vuori, M., van der Sluijs, P., Peranen, J. and Ikonen, E. (2007). Rab8-dependent recycling promotes endosomal cholesterol removal in normal and sphingolipidosis cells. Mol. Biol. Cell 18, 47-56.
Lombardi, D., Soldati, T., Riederer, M. A., Goda, Y., Zerial, M. and Pfeffer, S. R. (1993). Rab9 functions in transport between late endosomes and the trans Golgi network. EMBO J. 12, 677-682.[Medline]
Lütcke, A., Parton, R. G., Murphy, C., Olkkonen, V. M., Dupree, P., Valencia, A., Simons, K. and Zerial, M. (1994). Cloning and subcellular localization of novel rab proteins reveals polarized and cell type-specific expression. J. Cell Sci. 107, 3437-3448.[Abstract]
Markgraf, D. F., Peplowska, K. and Ungermann, C. (2007). Rab cascades and tethering factors in the endomembrane system. FEBS Lett. 581, 2125-2130.[CrossRef][Medline]
Martinez, O., Schmidt, A., Salamero, J., Hoflack, B., Roa, M. and Goud, B. (1994). The small GTP-binding protein rab6 functions in intra-Golgi transport. J. Cell Biol. 127, 1575-1588.
Marzesco, A. M., Dunia, I., Pandjaitan, R., Recouvreur, M., Dauzonne, D., Benedetti, E. L., Louvard, D. and Zahraoui, A. (2002). The small GTPase Rab13 regulates assembly of functional tight junctions in epithelial cells. Mol. Biol. Cell 13, 1819-1831.
Masuda, E. S., Luo, Y., Young, C., Shen, M., Rossi, A. B., Huang, B. C., Yu, S., Bennett, M. K., Payan, D. G. and Scheller, R. H. (2000). Rab37 is a novel mast cell specific GTPase localized to secretory granules. FEBS Lett. 470, 61-64.[CrossRef][Medline]
Mesa, R., Salomon, C., Roggero, M., Stahl, P. D. and Mayorga, L. S. (2001). Rab22a affects the morphology and function of the endocytic pathway. J. Cell Sci. 114, 4041-4049.[Medline]
Miaczynska, M., Christoforidis, S., Giner, A., Shevchenko, A., Uttenweiler-Joseph, S., Habermann, B., Wilm, M., Parton, R. G. and Zerial, M. (2004). APPL proteins link Rab5 to nuclear signal transduction via an endosomal compartment. Cell 116, 445-456.[CrossRef][Medline]
Mruk, D. D., Lau, A. S., Sarkar, O. and Xia, W. (2007). Rab4A GTPase–catenin interactions are involved in cell junction dynamics in the testis. J. Androl. 28, 742-754.
Munafó, D. B. and Colombo, M. I. (2002). Induction of autophagy causes dramatic changes in the subcellular distribution of GFP-Rab24. Traffic 3, 472-482.[CrossRef][Medline]
Nachury, M. V., Loktev, A. V., Zhang, Q., Westlake, C. J., Peranen, J., Merdes, A., Slusarski, D. C., Scheller, R. H., Bazan, J. F., Sheffield, V. C. et al. (2007). A core complex of BBS proteins cooperates with the GTPase Rab8 to promote ciliary membrane biogenesis. Cell 129, 1201-1213.[CrossRef][Medline]
Narita, K., Choudhury, A., Dobrenis, K., Sharma, D. K., Holicky, E. L., Marks, D. L., Walkley, S. U. and Pagano, R. E. (2005). Protein transduction of Rab9 in Niemann-Pick C cells reduces cholesterol storage. FASEB J. 19, 1558-1560.
Opdam, F. J., Echard, A., Croes, H. J., van den Hurk, J. A., van de Vorstenbosch, R. A., Ginsel, L. A., Goud, B. and Fransen, J. A. (2000). The small GTPase Rab6B, a novel Rab6 subfamily member, is cell-type specifically expressed and localised to the Golgi apparatus. J. Cell Sci. 113, 2725-2735.[Abstract]
Overmeyer, J. H. and Maltese, W. A. (2005). Tyrosine phosphorylation of Rab proteins. Meth. Enzymol. 403, 194-202.[Medline]
Ozeki, S., Cheng, J., Tauchi-Sato, K., Hatano, N., Taniguchi, H. and Fujimoto, T. (2005). Rab18 localizes to lipid droplets and induces their close apposition to the endoplasmic reticulum-derived membrane. J. Cell Sci. 118, 2601-2611.
Pelkmans, L., Burli, T., Zerial, M. and Helenius, A. (2004). Caveolin-stabilized membrane domains as multifunctional transport and sorting devices in endocytic membrane traffic. Cell 118, 767-780.[CrossRef][Medline]
Pellinen, T., Arjonen, A., Vuoriluoto, K., Kallio, K., Fransen, J. A. and Ivaska, J. (2006). Small GTPase Rab21 regulates cell adhesion and controls endosomal traffic of beta1-integrins. J. Cell Biol. 173, 767-780.
Peränen, J., Auvinen, P., Virta, H., Wepf, R. and Simons, K. (1996). Rab8 promotes polarized membrane transport through reorganization of actin and microtubules in fibroblasts. J. Cell Biol. 135, 153-167.
Pereira-Leal, J. B. and Seabra, M. C. (2000). The mammalian Rab family of small GTPases: definition of family and subfamily sequence motifs suggests a mechanism for functional specificity in the Ras superfamily. J. Mol. Biol. 301, 1077-1087.[CrossRef][Medline]
Pfeffer, S. R. (2005). Structural clues to Rab GTPase functional diversity. J. Biol. Chem. 280, 15485-15488.
Proikas-Cezanne, T., Gaugel, A., Frickey, T. and Nordheim, A. (2006). Rab14 is part of the early endosomal clathrin-coated TGN microdomain. FEBS Lett. 580, 5241-5246.[CrossRef][Medline]
Rak, A., Pylypenko, O., Niculae, A., Pyatkov, K., Goody, R. S. and Alexandrov, K. (2004). Structure of the Rab7:REP-1 complex: insights into the mechanism of Rab prenylation and choroideremia disease. Cell 117, 749-760.[CrossRef][Medline]
Roach, W. G., Chavez, J. A., Miinea, C. P. and Lienhard, G. E. (2007). Substrate specificity and effect on GLUT4 translocation of the Rab GTPase-activating protein Tbc1d1. Biochem. J. 403, 353-358.[CrossRef][Medline]
Roberts, E. A., Chua, J., Kyei, G. B. and Deretic, V. (2006). Higher order Rab programming in phagolysosome biogenesis. J. Cell Biol. 174, 923-929.
Rodriguez-Gabin, A. G., Cammer, M., Almazan, G., Charron, M. and Larocca, J. N. (2001). Role of rRAB22b, an oligodendrocyte protein, in regulation of transport of vesicles from trans Golgi to endocytic compartments. J. Neurosci. Res. 66, 1149-1160.[CrossRef][Medline]
Rupnik, M., Kreft, M., Nothias, F., Grilc, S., Bobanovic, L. K., Johannes, L., Kiauta, T., Vernier, P., Darchen, F. and Zorec, R. (2007). Distinct role of Rab3A and Rab3B in secretory activity of rat melanotrophs. Am. J. Physiol. Cell Physiol. 292, C98-C105.
Salminen, A. and Novick, P. J. (1987). A ras-like protein is required for a post-Golgi event in yeast secretion. Cell 49, 527-538.[CrossRef][Medline]
Schlüter, O. M., Khvotchev, M., Jahn, R. and Sudhof, T. C. (2002). Localization versus function of Rab3 proteins. Evidence for a common regulatory role in controlling fusion. J. Biol. Chem. 277, 40919-40929.
Schmitt, H. D., Wagner, P., Pfaff, E. and Gallwitz, D. (1986). The ras-related YPT1 gene product in yeast: a GTP-binding protein that might be involved in microtubule organization. Cell 47, 401-412.[CrossRef][Medline]
Schuck, S., Gerl, M. J., Ang, A., Manninen, A., Keller, P., Mellman, I. and Simons, K. (2007). Rab10 is involved in basolateral transport in polarized Madin-Darby canine kidney cells. Traffic 8, 47-60.[CrossRef][Medline]
Shan, J., Mason, J. M., Yuan, L., Barcia, M., Porti, D., Calabro, A., Budman, D., Vinciguerra, V. and Xu, H. (2000). Rab6c, a new member of the rab gene family, is involved in drug resistance in MCF7/AdrR cells. Gene 257, 67-75.[CrossRef][Medline]
Shin, H. W., Hayashi, M., Christoforidis, S., Lacas-Gervais, S., Hoepfner, S., Wenk, M. R., Modregger, J., Uttenweiler-Joseph, S., Wilm, M., Nystuen, A. et al. (2005). An enzymatic cascade of Rab5 effectors regulates phosphoinositide turnover in the endocytic pathway. J. Cell Biol. 170, 607-618.
Stein, M. P., Dong, J. and Wandinger-Ness, A. (2003). Rab proteins and endocytic trafficking: potential targets for therapeutic intervention. Adv. Drug Deliv. Rev. 55, 1421-1437.[CrossRef][Medline]
Stenmark, H. and Olkkonen, V. M. (2001). The Rab GTPase family. Genome Biol. 2, REVIEWS3007.[Medline]
Sun, P. and Endo, T. (2005). Assays for functional properties of Rab34 in macropinosome formation. Meth. Enzymol. 403, 229-243.[Medline]
Sun, P., Yamamoto, H., Suetsugu, S., Miki, H., Takenawa, T. and Endo, T. (2003). Small GTPase Rah/Rab34 is associated with membrane ruffles and macropinosomes and promotes macropinosome formation. J. Biol. Chem. 278, 4063-4071.
Tisdale, E. J., Bourne, J. R., Khosravi-Far, R., Der, C. J. and Balch, W. E. (1992). GTP-binding mutants of rab1 and rab2 are potent inhibitors of vesicular transport from the endoplasmic reticulum to the Golgi complex. J. Cell Biol. 119, 749-761.
Tolmachova, T., Abrink, M., Futter, C. E., Authi, K. S. and Seabra, M. C. (2007). Rab27b regulates number and secretion of platelet dense granules. Proc. Natl. Acad. Sci. USA 104, 5872-5877.
Touchot, N., Chardin, P. and Tavitian, A. (1987). Four additional members of the ras gene superfamily isolated by an oligonucleotide strategy: molecular cloning of YPT-related cDNAs from a rat brain library. Proc. Natl. Acad. Sci. USA 84, 8210-8214.
Tsuboi, T. and Fukuda, M. (2006). Rab3A and Rab27A cooperatively regulate the docking step of dense-core vesicle exocytosis in PC12 cells. J. Cell Sci. 119, 2196-2203.
Ullrich, O., Reinsch, S., Urbe, S., Zerial, M. and Parton, R. G. (1996). Rab11 regulates recycling through the pericentriolar recycling endosome. J. Cell Biol. 135, 913-924.
Valsdottir, R., Hashimoto, H., Ashman, K., Koda, T., Storrie, B. and Nilsson, T. (2001). Identification of rabaptin-5, rabex-5, and GM130 as putative effectors of rab33b, a regulator of retrograde traffic between the Golgi apparatus and ER. FEBS Lett. 508, 201-209.[CrossRef][Medline]
van der Sluijs, P., Hull, M., Webster, P., Male, P., Goud, B. and Mellman, I. (1992). The small GTP-binding protein rab4 controls an early sorting event on the endocytic pathway. Cell 70, 729-740.[CrossRef][Medline]
Vazquez-Martinez, R., Cruz-Garcia, D., Duran-Prado, M., Peinado, J. R., Castano, J. P. and Malagon, M. M. (2007). Rab18 inhibits secretory activity in neuroendocrine cells by interacting with secretory granules. Traffic 8, 867-882.[CrossRef][Medline]
Vitale, G., Rybin, V., Christoforidis, S., Thornqvist, P., McCaffrey, M., Stenmark, H. and Zerial, M. (1998). Distinct Rab-binding domains mediate the interaction of Rabaptin-5 with GTP-bound Rab4 and Rab5. EMBO J. 17, 1941-1951.[CrossRef][Medline]
Vonderheit, A. and Helenius, A. (2005). Rab7 associates with early endosomes to mediate sorting and transport of Semliki forest virus to late endosomes. PLoS Biol. 3, e233.[CrossRef][Medline]
Wang, X., Kumar, R., Navarre, J., Casanova, J. E. and Goldenring, J. R. (2000). Regulation of vesicle trafficking in madin-darby canine kidney cells by Rab11a and Rab25. J. Biol. Chem. 275, 29138-29146.
Wang, Y., Ng, E. L. and Tang, B. L. (2006). Rab23: what exactly does it traffic? Traffic 7, 746-750.[CrossRef][Medline]
Wang, Y., Chen, T., Han, C., He, D., Liu, H., An, H., Cai, Z. and Cao, X. (2007). Lysosome-associated small Rab GTPase Rab7b negatively regulates TLR4 signaling in macrophages by promoting lysosomal degradation of TLR4. Blood 110, 962-971.
Wasmeier, C., Romao, M., Plowright, L., Bennett, D. C., Raposo, G. and Seabra, M. C. (2006). Rab38 and Rab32 control post-Golgi trafficking of melanogenic enzymes. J. Cell Biol. 175, 271-281.
Wennerberg, K., Rossman, K. L. and Der, C. J. (2005). The Ras superfamily at a glance. J. Cell Sci. 118, 843-846.
Wilcke, M., Johannes, L., Galli, T., Mayau, V., Goud, B. and Salamero, J. (2000). Rab11 regulates the compartmentalization of early endosomes required for efficient transport from early endosomes to the trans-golgi network. J. Cell Biol. 151, 1207-1220.
Wu, M., Wang, T., Loh, E., Hong, W. and Song, H. (2005). Structural basis for recruitment of RILP by small GTPase Rab7. EMBO J. 24, 1491-1501.[CrossRef][Medline]
Wu, M., Yin, G., Zhao, X., Ji, C., Gu, S., Tang, R., Dong, H., Xie, Y. and Mao, Y. (2006). Human RAB24, interestingly and predominantly distributed in the nuclei of COS-7 cells, is colocalized with cyclophilin A and GABARAP. Int. J. Mol. Med. 17, 749-754.[Medline]
Yoshie, S., Imai, A., Nashida, T. and Shimomura, H. (2000). Expression, characterization, and localization of Rab26, a low molecular weight GTP-binding protein, in the rat parotid gland. Histochem. Cell Biol. 113, 259-263.[Medline]
Yu, X., Prekeris, R. and Gould, G. W. (2007). Role of endosomal Rab GTPases in cytokinesis. Eur. J. Cell Biol. 86, 25-35.[CrossRef][Medline]
Zacchi, P., Stenmark, H., Parton, R. G., Orioli, D., Lim, F., Giner, A., Mellman, I., Zerial, M. and Murphy, C. (1998). Rab17 regulates membrane trafficking through apical recycling endosomes in polarized epithelial cells. J. Cell Biol. 140, 1039-1053.
Zerial, M. and McBride, H. (2001). Rab proteins as membrane organizers. Nat. Rev. Mol. Cell Biol. 2, 107-117.[CrossRef][Medline]
Zuk, P. A. and Elferink, L. A. (2000). Rab15 differentially regulates early endocytic trafficking. J. Biol. Chem. 275, 26754-26764.
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