Clustering induces a lateral redistribution of alpha 2 beta 1 integrin from membrane rafts to caveolae and subsequent protein kinase C-dependent internalization

• Published in: Molecular biology of the cell 2004-02, Vol.15 (2), p.625-636
• Main Authors: Upla, Paula, Marjomäki, Varpu, Kankaanpää, Pasi, Ivaska, Johanna, Hyypiä, Timo, Van Der Goot, F Gisou, Heino, Jyrki
• Format: Article
• Language: English
• Subjects: Actin Cytoskeleton - metabolism; Caveolae - metabolism; Caveolin 1; Caveolins - metabolism; Cell Membrane - metabolism; Cell Membrane Structures - metabolism; Cells, Cultured; Coated Vesicles - metabolism; Endosomes - metabolism; Enterovirus B, Human - metabolism; Humans; Integrin alpha2beta1 - metabolism; Integrin alphaV - metabolism; Microscopy, Immunoelectron; Protein Kinase C - metabolism; Protein Kinase C-alpha
• ISSN: 1059-1524
• DOI: 10.1091/mbc.E03-08-0588

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.