Journal of Cell Science, Vol 107, Issue 7 1909-1920, Copyright © 1994 by Company of Biologists

JOURNAL ARTICLES

Molecular characterization of two functional domains of CLIP-170 in vivo

P Pierre, R Pepperkok and TE Kreis
Departement de Biologie Cellulaire, Sciences III, Universite, Geneve, Switzerland.

CLIP-170 is a microtubule-binding protein isolated from HeLa cells that is involved in the interaction of endosomes with microtubules. The basic N-terminal domain of CLIP-170 binds to microtubules in vitro. To characterize further the functional domains of this cytoplasmic linker protein, we have transiently expressed intact and mutant forms of CLIP-170 in mammalian cells (HeLa and Vero cells) and show that the tandem repeat present in the N-terminal domain is essential for its binding to microtubules in vivo as previously found in vitro. With increasing levels of expression of CLIP-170, the sites with which the peripheral ends of microtubules interact enlarge, eventually forming large patches, which finally lead to the apparent bundling of microtubules. These patches do not form when the C-terminal domain is absent from the transfected protein. Modification of the microtubule-binding region, particularly of the tandem repeat motif, modulates the binding of CLIP-170 to microtubules. Overexpressed CLIP-170 appears neither to interact with nor to influence the organization of the intermediate filaments, and collapsing the network of intermediate filaments with microinjected antibodies against vimentin has no effect on the distribution of CLIP-170. These data suggest that CLIP-170 has at least two functional domains in vivo, an N-terminal microtubule-binding domain, and a C-terminal domain that is involved in the anchoring of microtubules to peripheral cytoplasmic structures.

This article has been cited by other articles:

				J. Gao, L. Huo, X. Sun, M. Liu, D. Li, J.-T. Dong, and J. Zhou The Tumor Suppressor CYLD Regulates Microtubule Dynamics and Plays a Role in Cell Migration J. Biol. Chem., April 4, 2008; 283(14): 8802 - 8809. [Abstract] [Full Text] [PDF]

				A. Hoppeler-Lebel, C. Celati, G. Bellett, M. M. Mogensen, L. Klein-Hitpass, M. Bornens, and A.-M. Tassin Centrosomal CAP350 protein stabilises microtubules associated with the Golgi complex J. Cell Sci., September 15, 2007; 120(18): 3299 - 3308. [Abstract] [Full Text] [PDF]

				M. G. Binker, D. Y. Zhao, S. J. Y. Pang, and R. E. Harrison Cytoplasmic Linker Protein-170 Enhances Spreading and Phagocytosis in Activated Macrophages by Stabilizing Microtubules J. Immunol., September 15, 2007; 179(6): 3780 - 3791. [Abstract] [Full Text] [PDF]

				K. U. Hong, Y. S. Park, Y.-S. Seong, D. Kang, C.-D. Bae, and J. Park Functional Importance of the Anaphase-Promoting Complex-Cdh1-Mediated Degradation of TMAP/CKAP2 in Regulation of Spindle Function and Cytokinesis Mol. Cell. Biol., May 15, 2007; 27(10): 3667 - 3681. [Abstract] [Full Text] [PDF]

				G. Tian, M. C. Huang, R. Parvari, G. A. Diaz, and N. J. Cowan Cryptic out-of-frame translational initiation of TBCE rescues tubulin formation in compound heterozygous HRD PNAS, September 5, 2006; 103(36): 13491 - 13496. [Abstract] [Full Text] [PDF]

				A. Akhmanova, A.-L. Mausset-Bonnefont, W. van Cappellen, N. Keijzer, C. C. Hoogenraad, T. Stepanova, K. Drabek, J. van der Wees, M. Mommaas, J. Onderwater, et al. The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis Genes & Dev., October 15, 2005; 19(20): 2501 - 2515. [Abstract] [Full Text] [PDF]

				F. Bartolini, G. Tian, M. Piehl, L. Cassimeris, S. A. Lewis, and N. J. Cowan Identification of a novel tubulin-destabilizing protein related to the chaperone cofactor E J. Cell Sci., March 15, 2005; 118(6): 1197 - 1207. [Abstract] [Full Text] [PDF]

				V. Lallemand-Breitenbach, M. Quesnoit, V. Braun, A. El Marjou, C. Pous, B. Goud, and F. Perez CLIPR-59 Is a Lipid Raft-associated Protein Containing a Cytoskeleton-associated Protein Glycine-rich Domain (CAP-Gly) That Perturbs Microtubule Dynamics J. Biol. Chem., September 24, 2004; 279(39): 41168 - 41178. [Abstract] [Full Text] [PDF]

				G. Wieland, S. Orthaus, S. Ohndorf, S. Diekmann, and P. Hemmerich Functional Complementation of Human Centromere Protein A (CENP-A) by Cse4p from Saccharomyces cerevisiae Mol. Cell. Biol., August 1, 2004; 24(15): 6620 - 6630. [Abstract] [Full Text] [PDF]

				J. Andrade, H. Zhao, B. Titus, S. Timm Pearce, and M. Barroso The EF-Hand Ca2+-binding Protein p22 Plays a Role in Microtubule and Endoplasmic Reticulum Organization and Dynamics with Distinct Ca2+-binding Requirements Mol. Biol. Cell, February 1, 2004; 15(2): 481 - 496. [Abstract] [Full Text] [PDF]

				W. Bu and L.-K. Su Characterization of Functional Domains of Human EB1 Family Proteins J. Biol. Chem., December 12, 2003; 278(50): 49721 - 49731. [Abstract] [Full Text] [PDF]

				F. Kragler, M. Curin, K. Trutnyeva, A. Gansch, and E. Waigmann MPB2C, a Microtubule-Associated Plant Protein Binds to and Interferes with Cell-to-Cell Transport of Tobacco Mosaic Virus Movement Protein Plant Physiology, August 1, 2003; 132(4): 1870 - 1883. [Abstract] [Full Text] [PDF]

				T. Stepanova, J. Slemmer, C. C. Hoogenraad, G. Lansbergen, B. Dortland, C. I. De Zeeuw, F. Grosveld, G. van Cappellen, A. Akhmanova, and N. Galjart Visualization of Microtubule Growth in Cultured Neurons via the Use of EB3-GFP (End-Binding Protein 3-Green Fluorescent Protein) J. Neurosci., April 1, 2003; 23(7): 2655 - 2664. [Abstract] [Full Text] [PDF]

				L. A. Ligon, S. S. Shelly, M. Tokito, and E. L.F. Holzbaur The Microtubule Plus-End Proteins EB1 and Dynactin Have Differential Effects on Microtubule Polymerization Mol. Biol. Cell, April 1, 2003; 14(4): 1405 - 1417. [Abstract] [Full Text] [PDF]

				P. Dhonukshe and T. W. J. Gadella Jr. Alteration of Microtubule Dynamic Instability during Preprophase Band Formation Revealed by Yellow Fluorescent Protein-CLIP170 Microtubule Plus-End Labeling PLANT CELL, March 1, 2003; 15(3): 597 - 611. [Abstract] [Full Text] [PDF]

				U. Sahin, F. Neumann, O. Tureci, R. Schmits, F. Perez, and M. Pfreundschuh Hodgkin and Reed-Sternberg cell-associated autoantigen CLIP-170/restin is a marker for dendritic cells and is involved in the trafficking of macropinosomes to the cytoskeleton, supporting a function-based concept of Hodgkin and Reed-Sternberg cells Blood, December 1, 2002; 100(12): 4139 - 4145. [Abstract] [Full Text] [PDF]

				Y. A. Komarova, A. S. Akhmanova, S.-i. Kojima, N. Galjart, and G. G. Borisy Cytoplasmic linker proteins promote microtubule rescue in vivo J. Cell Biol., November 25, 2002; 159(4): 589 - 599. [Abstract] [Full Text] [PDF]

				F. M. Coquelle, M. Caspi, F. P. Cordelieres, J. P. Dompierre, D. L. Dujardin, C. Koifman, P. Martin, C. C. Hoogenraad, A. Akhmanova, N. Galjart, et al. LIS1, CLIP-170's Key to the Dynein/Dynactin Pathway Mol. Cell. Biol., May 1, 2002; 22(9): 3089 - 3102. [Abstract] [Full Text] [PDF]

				F. Perez, K. Pernet-Gallay, C. Nizak, H. V. Goodson, T. E. Kreis, and B. Goud CLIPR-59, a new trans-Golgi/TGN cytoplasmic linker protein belonging to the CLIP-170 family J. Cell Biol., February 18, 2002; 156(4): 631 - 642. [Abstract] [Full Text] [PDF]

				A Habermann, T. Schroer, G Griffiths, and J. Burkhardt Immunolocalization of cytoplasmic dynein and dynactin subunits in cultured macrophages: enrichment on early endocytic organelles J. Cell Sci., January 1, 2001; 114(1): 229 - 240. [Abstract] [PDF]

				C. Hoogenraad, A Akhmanova, F Grosveld, C. De Zeeuw, and N Galjart Functional analysis of CLIP-115 and its binding to microtubules J. Cell Sci., January 6, 2000; 113(12): 2285 - 2297. [Abstract] [PDF]

				C. Valetti, D. M. Wetzel, M. Schrader, M. J. Hasbani, S. R. Gill, T. E. Kreis, and T. A. Schroer Role of Dynactin in Endocytic Traffic: Effects of Dynamitin Overexpression and Colocalization with CLIP-170 Mol. Biol. Cell, December 1, 1999; 10(12): 4107 - 4120. [Abstract] [Full Text]

				J. Scheel, P. Pierre, J. E. Rickard, G. S. Diamantopoulos, C. Valetti, F. G. van der Goot, M. Haner, U. Aebi, and T. E. Kreis Purification and Analysis of Authentic CLIP-170 and Recombinant Fragments J. Biol. Chem., September 3, 1999; 274(36): 25883 - 25891. [Abstract] [Full Text] [PDF]

				G. S. Diamantopoulos, F. Perez, H. V. Goodson, G. Batelier, R. Melki, T. E. Kreis, and J. E. Rickard Dynamic Localization of CLIP-170 to Microtubule Plus Ends Is Coupled to Microtubule Assembly J. Cell Biol., January 11, 1999; 144(1): 99 - 112. [Abstract] [Full Text] [PDF]

				B. Feierbach, E. Nogales, K. H. Downing, and T. Stearns Alf1p, a CLIP-170 Domain-containing Protein, Is Functionally and Physically Associated with alpha -Tubulin J. Cell Biol., January 11, 1999; 144(1): 113 - 124. [Abstract] [Full Text] [PDF]

				I. Clark and D. Meyer Overexpression of normal and mutant Arp1alpha (centractin) differentially affects microtubule organization during mitosis and interphase J. Cell Sci., January 10, 1999; 112(20): 3507 - 3518. [Abstract] [PDF]

				K. Vaughan, S. Tynan, N. Faulkner, C. Echeverri, and R. Vallee Colocalization of cytoplasmic dynein with dynactin and CLIP-170 at microtubule distal ends J. Cell Sci., January 5, 1999; 112(10): 1437 - 1447. [Abstract] [PDF]

				J. A. Kahana, G. Schlenstedt, D. M. Evanchuk, J. R. Geiser, M. A. Hoyt, and P. A. Silver The Yeast Dynactin Complex Is Involved in Partitioning the Mitotic Spindle between Mother and Daughter Cells during Anaphase B Mol. Biol. Cell, July 1, 1998; 9(7): 1741 - 1756. [Abstract] [Full Text]

				D. Dujardin, U. I. Wacker, A. Moreau, T. A. Schroer, J. E. Rickard, and J. R. De Mey Evidence for a Role of CLIP-170 in the Establishment of Metaphase Chromosome Alignment J. Cell Biol., May 18, 1998; 141(4): 849 - 862. [Abstract] [Full Text] [PDF]

				V. A. Lantz and K. G. Miller A Class VI Unconventional Myosin Is Associated with a Homologue of a Microtubule-binding Protein, Cytoplasmic Linker Protein-170, in Neurons and at the Posterior Pole of Drosophila Embryos J. Cell Biol., February 23, 1998; 140(4): 897 - 910. [Abstract] [Full Text] [PDF]

				R Pepperkok, M Lowe, B Burke, and T. Kreis Three distinct steps in transport of vesicular stomatitis virus glycoprotein from the ER to the cell surface in vivo with differential sensitivities to GTP gamma S J. Cell Sci., January 7, 1998; 111(13): 1877 - 1888. [Abstract] [PDF]

				N. Ulitzur, C. Rancano, and S. R. Pfeffer Biochemical Characterization Of Mapmodulin, a Protein That Binds Microtubule-associated Proteins J. Biol. Chem., November 28, 1997; 272(48): 30577 - 30582. [Abstract] [Full Text] [PDF]

				J. Scheel, R. Pepperkok, M. Lowe, G. Griffiths, and T. E. Kreis Dissociation of Coatomer from Membranes Is Required for Brefeldin A-induced Transfer of Golgi Enzymes to the Endoplasmic Reticulum J. Cell Biol., April 21, 1997; 137(2): 319 - 333. [Abstract] [Full Text] [PDF]

				L. Ling and D. V. Goeddel MIP-T3, a Novel Protein Linking Tumor Necrosis Factor Receptor-associated Factor 3 to the Microtubule Network J. Biol. Chem., July 28, 2000; 275(31): 23852 - 23860. [Abstract] [Full Text] [PDF]

				H. Lin, P. de Carvalho, D. Kho, C.-Y. Tai, P. Pierre, G. R. Fink, and D. Pellman Polyploids require Bik1 for kinetochore-microtubule attachment J. Cell Biol., December 24, 2001; 155(7): 1173 - 1184. [Abstract] [Full Text] [PDF]

				F. Perez, K. Pernet-Gallay, C. Nizak, H. V. Goodson, T. E. Kreis, and B. Goud CLIPR-59, a new trans-Golgi/TGN cytoplasmic linker protein belonging to the CLIP-170 family J. Cell Biol., February 18, 2002; 156(4): 631 - 642. [Abstract] [Full Text] [PDF]