Clustering induces a lateral redistribution of alpha 2 beta 1 integrin from membrane rafts to caveolae and subsequent protein kinase C-dependent internalization.
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.
Upla
Paula
P
Cell Biology, University of Jyväskylä, FIN-40351 Jyväskylä, Finland.
Marjomäki
Varpu
V
Kankaanpää
Pasi
P
Ivaska
Johanna
J
Hyypiä
Timo
T
Van Der Goot
F Gisou
FG
Heino
Jyrki
J
D008841:Actin Cytoskeleton / Q000378:metabolism; D021941:Caveolae / Q000378:metabolism*; D051242:Caveolin 1; D022461:Caveolins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D021961:Cell Membrane Structures / Q000378:metabolism*; D002478:Cells, Cultured; D018699:Coated Vesicles / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D029822:Enterovirus B, Human / Q000378:metabolism; D006801:Humans; D038982:Integrin alpha2beta1 / Q000378:metabolism*; D039564:Integrin alphaV / Q000378:metabolism; D016253:Microscopy, Immunoelectron; D011493:Protein Kinase C / Q000378:metabolism*; D051571:Protein Kinase C-alpha
C495540:CAV1 protein, human; D051242:Caveolin 1; D022461:Caveolins; D038982:Integrin alpha2beta1; D039564:Integrin alphaV; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha