Abstract：
:Kindlin-2 is a FERM and PH domain-containing integrin-binding protein that is emerging as an important regulator of integrin activation. How kindlin-2 functions in integrin activation, however, is not known. We report here that kindlin-2 interacts with multiple phosphoinositides, preferentially with phosphatidylinositol 3,4,5-trisphosphate. Although integrin-binding is essential for focal adhesion localization of kindlin-2, phosphoinositide-binding is not required for this process. Using biologically and clinically relevant glomerular podocytes as a model system, we show that integrin activation and dependent processes are tightly regulated by kindlin-2: depletion of kindlin-2 reduced integrin activation, matrix adhesion and fibronectin matrix deposition, whereas overexpression of kindlin-2 promoted these processes. Furthermore, we provide evidence showing that kindlin-2 is involved in phosphoinositide-3-kinase-mediated regulation of podocyte-matrix adhesion and fibronectin matrix deposition. Mechanistically, kindlin-2 promotes integrin activation and integrin-dependent processes through interacting with both integrins and phosphoinositides. TGF-β1, a mediator of progressive glomerular failure, markedly increased the level of kindlin-2 and fibronectin matrix deposition, and the latter process was reversed by depletion of kindlin-2. Our results reveal important functions of kindlin-2 in the regulation of podocyte-matrix adhesion and matrix deposition and shed new light on the mechanism whereby kindlin-2 functions in these processes.
journal_name
J Cell Scijournal_title
Journal of cell scienceauthors
Qu H,Tu Y,Shi X,Larjava H,Saleem MA,Shattil SJ,Fukuda K,Qin J,Kretzler M,Wu Cdoi
10.1242/jcs.076976subject
Has Abstractpub_date
2011-03-15 00:00:00pages
879-91issue
Pt 6eissn
0021-9533issn
1477-9137pii
jcs.076976journal_volume
124pub_type
杂志文章abstract：:We have isolated a fourth myosin gene (MYO4) in yeast (Saccharomyces cerevisiae). MYO4 encodes a approximately 170 kDa (1471 amino acid) class V myosin, using the classification devised by Cheney et al. (1993a; Cell Motil. Cytoskel. 24, 215-223); the motor domain is followed by a neck region containing six putative ca...
journal_title：Journal of cell science
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doi：
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journal_title：Journal of cell science
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journal_title：Journal of cell science
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更新日期：1996-09-01 00:00:00
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doi：
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