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Vol. 15, Issue 2, 625-636, February 2004
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2
1 Integrin from Membrane Rafts to Caveolae and Subsequent Protein Kinase C-dependent Internalization
* Cell Biology, University of Jyväskylä, FIN-40351 Jyväskylä, Finland;
VTT Medical Biotechnology, FIN-20520 Turku, Finland;
Department of Microbiology, University of Oulu, FIN-90220 Oulu, Finland; and
Department of Genetics and Microbiology, University of Geneva, 1211 Geneva 4, Switzerland
Submitted August 13, 2003;
Revised October 29, 2003;
Accepted November 13, 2003
Monitoring Editor: Carl-Henrik Heldin
Integrin 
2
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 21 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 21 integrin, they started to move laterally on cell surface along actin filaments. During the lateral movement small clusters fused together. Finally 21 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 activity. Caveolae are known to be highly immobile structures and 21 integrin clusters represent a previously unknown mechanism to activate endocytic trafficking via caveolae. The process was specific to 21 integrin, because the antibody-mediated formation of 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 21 and taking advantage of 21 internalization via caveolae.
Abbreviations used: CA, constitutively active; DN, dominant negative; DRM, detergent resistant membranes; EEA1, early endosome associated protein; ERK, extracellular signal regulated kinase; EV1, echovirus-1; GPI-APs, glycosyl phosphatidyl inositol anchored proteins; MAPK, mitogen activated protein kinase; MOI, multiplicity of infection; PKC, protein kinase C; SV40, simian virus 40.
¶ Corresponding author. E-mail address: jyrki.heino{at}utu.fi.
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