Involvement of nectin in inactivation of integrin alpha vbeta 3 after the establishment of cell-cell adhesion

Sakamoto Y, Ogita H, Komura H, Takai Y
Source: J Biol Chem
Publication Date: (2008)
Issue: 283(1): 496-505
Research Area:
Cancer Research/Cell Biology
Cells used in publication:
Species: canine
Tissue Origin: kidney
Nucleofector® I/II/2b
Integrin plays an essential role in the formation of cell-matrix junctions and is also involved in the fundamental cellular functions. In the process of the formation of cell-cell junctions, an immunoglobulin-like cell-cell adhesion molecule (CAM) nectin initially trans-interacts together and promotes the formation of adherens junctions (AJs) cooperatively with another CAM cadherin. The activation of integrin alphavbeta3 is critically necessary for this nectin-induced formation of AJs. However, after the establishment of AJs, integrin alphavbeta3 becomes inactive and retains the association with nectin at AJs. The molecular mechanism of this dynamic regulation of integrin alphavbeta3 during the formation of AJs remains unclear. We found here that the expression of phosphatidylinositol phosphate kinase type Igamma90 (PIPKIgamma90), which is involved in the regulation of integrin activation, in MDCK cells preferentially reversed the inactivation of integrin alphavbeta3 at cell-cell adhesion sites and partially disrupted E-cadherin-based AJs. The activation of PIPKIgamma is correlated with its phosphorylation state. The tyrosine phosphatase protein tyrosine phosphatase mu (PTPmu) effectively de-phosphorylated PIPKIgamma and thus canceled the PIPKIgamma-dependent activation of integrin alphavbeta3 by blocking the interaction of integrin alphavbeta3 with talin. Moreover, PTPmu associated with nectin and its phosphatase activity was enhanced by the trans-interaction of nectin, leading to the decrease in PIPKIgamma90 phosphorylation. Therefore, the trans-interaction of nectin essentially functions in the inactivation of integrin at AJs through the PTPmu-induced inactivation of PIPKIgamma.