PDGF-regulated rab4-dependent recycling of αvβ3 integrin from early endosomes is necessary for cell adhesion and spreading
| Autor: | Peter van der Sluijs, Marnie S. Roberts, Simon T. Barry, Jim C. Norman, Alison J. Woods |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Endosome
Integrin Becaplermin Endosomes Endocytosis General Biochemistry Genetics and Molecular Biology Exocytosis Mice 03 medical and health sciences Receptors Fibronectin 0302 clinical medicine Cell Movement Cell Adhesion Image Processing Computer-Assisted Animals Receptors Vitronectin Cell adhesion 030304 developmental biology Platelet-Derived Growth Factor 0303 health sciences Agricultural and Biological Sciences(all) biology rab4 GTP-Binding Proteins Biochemistry Genetics and Molecular Biology(all) Cell adhesion molecule 3T3 Cells Proto-Oncogene Proteins c-sis Cell biology Fibronectin 030220 oncology & carcinogenesis biology.protein Rab General Agricultural and Biological Sciences |
| Zdroj: | Current Biology. 11:1392-1402 |
| ISSN: | 0960-9822 |
| DOI: | 10.1016/s0960-9822(01)00442-0 |
| Popis: | It has been postulated that the regulation of integrin vesicular traffic facilitates cell migration by internalizing integrins at the rear of the cell and transporting them forward within vesicles for exocytosis at the leading edge to form new contacts with the extracellular matrix. The rab family of GTPases control key targeting events in the endo/exocytic pathway; therefore, these GTPases may be involved in the regulation of cell-matrix contact assembly.The endo/exocytic cycle of alphavbeta3 and alpha5beta1 integrins was studied using mouse 3T3 fibroblast cell lines. In serum-starved cells, internalized integrins were transported through rab4-positive, early endosomes and arrived at the rab11-positive, perinuclear recycling compartment approximately 30 min after endocytosis. From the recycling compartment, integrins were recycled to the plasma membrane in a rab11-dependent fashion. Following treatment with PDGF, alphavbeta3 integrin, but not alpha5beta1, was rapidly recycled directly back to the plasma membrane from the early endosomes via a rab4-dependent mechanism without the involvement of rab11. This rapid recycling pathway directed alphavbeta3 to numerous small puncta distributed evenly across the dorsal surface of the cell, and the integrin only became localized into focal complexes at later times following PDGF addition. Interestingly, inhibition of PDGF-stimulated alphavbeta3 recycling using dominant-negative rab4 mutants compromised cell adhesion and spreading on vitronectin (a ligand for alphavbeta3), but adhesion to fibronectin (a ligand for alpha5beta1 and alphavbeta3) was unchanged.We propose that growth factor-regulated, rab4-dependent recycling of alphavbeta3 integrin from early endosomes to the plasma membrane is a critical upstream event in the assembly of cell-matrix contacts. |
| Databáze: | OpenAIRE |
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