Clustering induces a lateral redistribution of alpha 2 beta 1 integrin from membrane rafts to caveolae and subsequent protein kinase C-dependent internalization
- PMID: 14657242
- PMCID: PMC329276
- DOI: 10.1091/mbc.e03-08-0588
Clustering induces a lateral redistribution of alpha 2 beta 1 integrin from membrane rafts to caveolae and subsequent protein kinase C-dependent internalization
Abstract
Integrin alpha 2 beta 1 mediates the binding of several epithelial and mesenchymal cell types to collagen. The composition of the surrounding plasma membrane, especially caveolin-1- and cholesterol-containing membrane structures called caveolae, may be important to integrin signaling. On cell surface alpha 2 beta 1 integrin was located in the raft like membrane domain, rich in GPI-anchored proteins, rather than in caveolae. However, when antibodies were used to generate clusters of alpha 2 beta 1 integrin, they started to move laterally on cell surface along actin filaments. During the lateral movement small clusters fused together. Finally alpha 2 beta 1 integrin was found inside caveolae and subsequently internalized into caveosome-like perinuclear structures. The internalization process, unlike cluster formation or lateral redistribution, was dependent on protein kinase C alpha activity. Caveolae are known to be highly immobile structures and alpha 2 beta 1 integrin clusters represent a previously unknown mechanism to activate endocytic trafficking via caveolae. The process was specific to alpha 2 beta 1 integrin, because the antibody-mediated formation of alpha V integrin clusters activated their internalization in coated vesicles and early endosomes. In addition to natural ligands human echovirus-1 (EV1) gains entry into the cell by binding to alpha 2 beta 1 and taking advantage of alpha 2 beta 1 internalization via caveolae.
Figures
![Figure 5.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/329276/bin/zmk0030425330005.gif)
![Figure 6.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/329276/bin/zmk0030425330006.gif)
![Figure 7.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/329276/bin/zmk0030425330007.gif)
![Figure 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/329276/bin/zmk0030425330001.gif)
![Figure 2.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/329276/bin/zmk0030425330002.gif)
![Figure 3.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/329276/bin/zmk0030425330003.gif)
![Figure 4.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/329276/bin/zmk0030425330004.gif)
![Figure 8.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/329276/bin/zmk0030425330008.gif)
Similar articles
-
A Raft-derived, Pak1-regulated entry participates in alpha2beta1 integrin-dependent sorting to caveosomes.Mol Biol Cell. 2008 Jul;19(7):2857-69. doi: 10.1091/mbc.e07-10-1094. Epub 2008 Apr 30. Mol Biol Cell. 2008. PMID: 18448666 Free PMC article.
-
Internalization of echovirus 1 in caveolae.J Virol. 2002 Feb;76(4):1856-65. doi: 10.1128/jvi.76.4.1856-1865.2002. J Virol. 2002. PMID: 11799180 Free PMC article.
-
Cholesterol dependence of collagen and echovirus 1 trafficking along the novel α2β1 integrin internalization pathway.PLoS One. 2013;8(2):e55465. doi: 10.1371/journal.pone.0055465. Epub 2013 Feb 5. PLoS One. 2013. PMID: 23393580 Free PMC article.
-
Caveosomes and endocytosis of lipid rafts.J Cell Sci. 2003 Dec 1;116(Pt 23):4707-14. doi: 10.1242/jcs.00840. J Cell Sci. 2003. PMID: 14600257 Review.
-
Caveolae/raft-dependent endocytosis.J Cell Biol. 2003 May 26;161(4):673-7. doi: 10.1083/jcb.200302028. J Cell Biol. 2003. PMID: 12771123 Free PMC article. Review.
Cited by
-
Ligand-bound integrin αvβ6 internalisation and trafficking.Front Cell Dev Biol. 2022 Aug 24;10:920303. doi: 10.3389/fcell.2022.920303. eCollection 2022. Front Cell Dev Biol. 2022. PMID: 36092709 Free PMC article.
-
Membrane Rafts: Portals for Viral Entry.Front Microbiol. 2021 Feb 4;12:631274. doi: 10.3389/fmicb.2021.631274. eCollection 2021. Front Microbiol. 2021. PMID: 33613502 Free PMC article. Review.
-
Cholesterol-Rich Lipid Rafts in the Cellular Membrane Play an Essential Role in Avian Reovirus Replication.Front Microbiol. 2020 Nov 2;11:597794. doi: 10.3389/fmicb.2020.597794. eCollection 2020. Front Microbiol. 2020. PMID: 33224131 Free PMC article.
-
Coordinating Cytoskeleton and Molecular Traffic in T Cell Migration, Activation, and Effector Functions.Front Cell Dev Biol. 2020 Oct 21;8:591348. doi: 10.3389/fcell.2020.591348. eCollection 2020. Front Cell Dev Biol. 2020. PMID: 33195256 Free PMC article. Review.
-
A functionally neutral single chain antibody to measure beta-1 integrin uptake and recycling.Traffic. 2020 Sep;21(9):590-602. doi: 10.1111/tra.12754. Epub 2020 Jul 21. Traffic. 2020. PMID: 32613646 Free PMC article.
References
-
- Akula, S.M., Pramod, N.P., Wang, F.Z., and Chandran, B. (2002). Integrin α3β1 (CD 49c/29) is a cellular receptor for Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8) entry into the target cells. Cell 108, 407-419. - PubMed
-
- Benmerah, A., Bayrou, M., Cerf-Bensussan, N., and Dautry-Varsat, A. (1999). Inhibition of clathrin-coated pit assembly by an Eps15 mutant. J. Cell Sci. 112, 1303-1311. - PubMed
-
- Bergelson, J.M., Shepley, M.P., Chan, B.M., Hemler, M.E., and Finberg, R.W. (1992). Identification of the integrin VLA-2 as a receptor for echovirus 1. Science 255, 1718-1720. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Miscellaneous