TY - JOUR
T1 - Vinculin acts as a sensor in lipid regulation of adhesion-site turnover
AU - Chandrasekar, Indra
AU - Stradal, Theresia E.B.
AU - Holt, Mark R.
AU - Entschladen, Frank
AU - Jockusch, Brigitte M.
AU - Ziegler, Wolfgang H.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/4/1
Y1 - 2005/4/1
N2 - The dynamics of cell adhesion sites control cell morphology and motility. Adhesion-site turnover is thought to depend on the local availability of the acidic phospholipid phosphatidylinositol-4,5-bisphosphate (PIP2). PIP2 can bind to many cell adhesion proteins such as vinculin and talin, but the consequences of this interaction are poorly understood. To study the significance of phospholipid binding to vinculin for adhesion-site turnover and cell motility, we constructed a mutant, vinculin-LD, deficient in acidic phospholipid binding yet with functional actin-binding sites. When expressed in cells, vinculin-LD was readily recruited to adhesion sites, as judged by fluorescence recovery after photobleaching (FRAP) analysis, but cell spreading and migration were strongly impaired, and PIP2-dependent disassembly of adhesions was suppressed. Thus, PIP2 binding is not essential for vinculin activation and recruitment, as previously suggested. Instead, we propose that PIP2 levels can regulate the uncoupling of adhesion sites from the actin cytoskeleton, with vinculin functioning as a sensor.
AB - The dynamics of cell adhesion sites control cell morphology and motility. Adhesion-site turnover is thought to depend on the local availability of the acidic phospholipid phosphatidylinositol-4,5-bisphosphate (PIP2). PIP2 can bind to many cell adhesion proteins such as vinculin and talin, but the consequences of this interaction are poorly understood. To study the significance of phospholipid binding to vinculin for adhesion-site turnover and cell motility, we constructed a mutant, vinculin-LD, deficient in acidic phospholipid binding yet with functional actin-binding sites. When expressed in cells, vinculin-LD was readily recruited to adhesion sites, as judged by fluorescence recovery after photobleaching (FRAP) analysis, but cell spreading and migration were strongly impaired, and PIP2-dependent disassembly of adhesions was suppressed. Thus, PIP2 binding is not essential for vinculin activation and recruitment, as previously suggested. Instead, we propose that PIP2 levels can regulate the uncoupling of adhesion sites from the actin cytoskeleton, with vinculin functioning as a sensor.
KW - 5-bisphosphate
KW - Cell motility
KW - Cell-matrix adhesion
KW - Microfilaments
KW - Phosphatidylinositol-4
KW - Vinculin
UR - http://www.scopus.com/inward/record.url?scp=17844392639&partnerID=8YFLogxK
U2 - 10.1242/jcs.01734
DO - 10.1242/jcs.01734
M3 - Article
C2 - 15769850
AN - SCOPUS:17844392639
SN - 0021-9533
VL - 118
SP - 1461
EP - 1472
JO - Journal of Cell Science
JF - Journal of Cell Science
IS - 7
ER -