|
|
|
|
|
|
|
|
|||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | |||||
First published online June 28, 2004
doi: 10.1242/10.1242/jcs.01190
Research Article |
1 Angiogenesis Research Center and Section of Cardiology, Department of Medicine and Department of Pharmacology and Toxicology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA
2 Department of Pathology, Dartmouth Medical School, One Medical Center Drive, Lebanon, NH 03756, USA
* Author for correspondence (e-mail: michael.simons{at}dartmouth.edu)
Accepted 26 February 2004
Full activity of fibroblast growth factors (FGFs) requires their internalization in addition to the interaction with cell surface receptors. Recent studies have suggested that the transmembrane proteoglycan syndecan-4 functions as a FGF2 receptor. In this study we investigated the molecular basis of syndecan endocytosis and its role in FGF2 internalization in endothelial cells. We found that syndecan-4 uptake, induced either by treatment with FGF2 or by antibody clustering, requires the integrity of plasma membrane lipid rafts for its initiation, occurs in a non-clathrin-, non-dynamin-dependent manner and involves Rac1, which is activated by syndecan-4 clustering. FGF2 was internalized in a complex with syndecan-4 in 70 kDa dextran-containing endocytic vesicles. FGF2 and syndecan-4 but not dextran endocytosis were blocked by the dominant negative Rac1 while amiloride and the dominant-negative Cdc42 blocked internalization of dextran in addition to FGF2 and syndecan-4. Taken together, these results demonstrate that FGF2 endocytosis requires syndecan-4 clustering-dependent activation of Rac1 and the intact CDC42-dependent macropinocytic pathway.
Key words: Rac1, Macropinocytosis, Heparan sulfate, Growth factors, Signaling
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati 
Twitter What's this?
This article has been cited by other articles:
|
|
 |
|
  A. Wittrup, S.-H. Zhang, G. B. ten Dam, T. H. van Kuppevelt, P. Bengtson, M. Johansson, J. Welch, M. Morgelin, and M. Belting ScFv Antibody-induced Translocation of Cell-surface Heparan Sulfate Proteoglycan to Endocytic Vesicles: EVIDENCE FOR HEPARAN SULFATE EPITOPE SPECIFICITY AND ROLE OF BOTH SYNDECAN AND GLYPICAN J. Biol. Chem., November 20, 2009; 284(47): 32959 - 32967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. V. Andreeva, M. A. Kutuzov, V. A. Tkachuk, and T. A. Voyno-Yasenetskaya T-cadherin is located in the nucleus and centrosomes in endothelial cells Am J Physiol Cell Physiol, November 1, 2009; 297(5): C1168 - C1177. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Xu, Y. H. Zhang, M. Thangavel, M. M. Richardson, L. Liu, B. Zhou, Y. Zheng, R. S. Ostrom, and X. A. Zhang CD82 endocytosis and cholesterol-dependent reorganization of tetraspanin webs and lipid rafts FASEB J, October 1, 2009; 23(10): 3273 - 3288. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. J. Williams Some Things Just Have to Be Done In Vivo: GPIHBP1, Caloric Delivery, and the Generation of Remnant Lipoproteins Arterioscler Thromb Vasc Biol, June 1, 2009; 29(6): 792 - 795. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. B. Boyanovsky, P. Shridas, M. Simons, D. R. van der Westhuyzen, and N. R. Webb Syndecan-4 mediates macrophage uptake of group V secretory phospholipase A2-modified LDL J. Lipid Res., April 1, 2009; 50(4): 641 - 650. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Ramseger, R. White, and S. Kroger Transmembrane Form Agrin-induced Process Formation Requires Lipid Rafts and the Activation of Fyn and MAPK J. Biol. Chem., March 20, 2009; 284(12): 7697 - 7705. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Kuriyama and R. Mayor A role for Syndecan-4 in neural induction involving ERK- and PKC-dependent pathways Development, February 15, 2009; 136(4): 575 - 584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Hahn, A. Birkmann, E. Wies, D. Dorer, K. Mahr, M. Sturzl, F. Titgemeyer, and F. Neipel Kaposi's Sarcoma-Associated Herpesvirus gH/gL: Glycoprotein Export and Interaction with Cellular Receptors J. Virol., January 1, 2009; 83(1): 396 - 407. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Salikhova, L. Wang, A. A. Lanahan, M. Liu, M. Simons, W. P. J. Leenders, D. Mukhopadhyay, and A. Horowitz Vascular Endothelial Growth Factor and Semaphorin Induce Neuropilin-1 Endocytosis via Separate Pathways Circ. Res., September 12, 2008; 103(6): e71 - e79. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Murakami, A. Elfenbein, and M. Simons Non-canonical fibroblast growth factor signalling in angiogenesis Cardiovasc Res, May 1, 2008; 78(2): 223 - 231. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Paris, A. Burlacu, and Y. Durocher Opposing Roles of Syndecan-1 and Syndecan-2 in Polyethyleneimine-mediated Gene Delivery J. Biol. Chem., March 21, 2008; 283(12): 7697 - 7704. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Pape, B. H. Rauch, A. C. Rosenkranz, G. Kaber, and K. Schror Transcriptional Inhibition of Protease-Activated Receptor-1 Expression by Prostacyclin in Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): 534 - 540. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. D. Nascimento, M. A. F. Hayashi, A. Kerkis, V. Oliveira, E. B. Oliveira, G. Radis-Baptista, H. B. Nader, T. Yamane, I. L. dos Santos Tersariol, and I. Kerkis Crotamine Mediates Gene Delivery into Cells through the Binding to Heparan Sulfate Proteoglycans J. Biol. Chem., July 20, 2007; 282(29): 21349 - 21360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. G. Khan, J. Pichler, A. Rosemann, and D. Blaas Human Rhinovirus Type 54 Infection via Heparan Sulfate Is Less Efficient and Strictly Dependent on Low Endosomal pH J. Virol., May 1, 2007; 81(9): 4625 - 4632. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. H. Rauch, G. A. Scholz, D. Baumgartel-Allekotte, P. Censarek, J. W. Fischer, A.-A. Weber, and K. Schror Cholesterol Enhances Thrombin-Induced Release of Fibroblast Growth Factor-2 in Human Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, April 1, 2007; 27(4): e20 - e25. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tkachenko, A. Elfenbein, D. Tirziu, and M. Simons Syndecan-4 Clustering Induces Cell Migration in a PDZ-Dependent Manner Circ. Res., June 9, 2006; 98(11): 1398 - 1404. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. V. Stan Endocytosis pathways in endothelium: how many? Am J Physiol Lung Cell Mol Physiol, May 1, 2006; 290(5): L806 - L808. [Full Text] [PDF]
|
|
|
|
 |
|
 N. C. Gauthier, P. Monzo, V. Kaddai, A. Doye, V. Ricci, and P. Boquet Helicobacter pylori VacA Cytotoxin: A Probe for a Clathrin-independent and Cdc42-dependent Pinocytic Pathway Routed to Late Endosomes Mol. Biol. Cell, October 1, 2005; 16(10): 4852 - 4866. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Yufu, K. Hirano, D. Bi, M. Hirano, J. Nishimura, Y. Iwamoto, and H. Kanaide Rac1 Regulation of Surface Expression of Protease-Activated Receptor-1 and Responsiveness to Thrombin in Vascular Smooth Muscle Cells Arterioscler Thromb Vasc Biol, July 1, 2005; 25(7): 1506 - 1511. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Tkachenko, J. M. Rhodes, and M. Simons Syndecans: New Kids on the Signaling Block Circ. Res., March 18, 2005; 96(5): 488 - 500. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Vanlandschoot, F. Van Houtte, B. Serruys, and G. Leroux-Roels The arginine-rich carboxy-terminal domain of the hepatitis B virus core protein mediates attachment of nucleocapsids to cell-surface-expressed heparan sulfate J. Gen. Virol., January 1, 2005; 86(1): 75 - 84. [Abstract] [Full Text] [PDF]
|
|
