Clustering induces a lateral redistribution of α2β1 integrin from membrane rafts to caveolae and subsequent protein kinase C-dependent internalization

Paula Upla, Varpu Marjomäki, Pasi Kankaanpää, Johanna Ivaska, Timo Hyypiä, F. Gisou van der Goot, Jyrki Heino

Research output: Contribution to journalArticleScientificpeer-review

141 Citations (Scopus)

Abstract

Integrin α2β1 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 α2β1 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 α2β1 integrin, they started to move laterally on cell surface along actin filaments. During the lateral movement small clusters fused together. Finally α2β1 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 Cα activity. Caveolae are known to be highly immobile structures and α2β1 integrin clusters represent a previously unknown mechanism to activate endocytic trafficking via caveolae. The process was specific to α2β1 integrin, because the antibody-mediated formation of αV 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 α2β1 and taking advantage of α2β1 internalization via caveolae.
Original languageEnglish
Pages (from-to)625-636
JournalMolecular Biology of the Cell
Volume15
Issue number2
DOIs
Publication statusPublished - 2004
MoE publication typeA1 Journal article-refereed

Keywords

  • integrin
  • caveolae
  • kinase
  • proteins
  • antibodies

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