CD151 regulates epithelial cell-cell adhesion through PKC- and Cdc42-dependent actin cytoskeletal reorganization.
CD151, a member of the tetraspanin family proteins, tightly associates with integrin alpha3beta1 and localizes at basolateral surfaces of epithelial cells. We found that overexpression of CD151 in A431 cells accelerated intercellular adhesion, whereas treatment of cells with anti-CD151 mAb perturbed the integrity of cortical actin filaments and cell polarity. E-Cadherin puncta formation, indicative of filopodia-based adhesion zipper formation, as well as E-cadherin anchorage to detergent-insoluble cytoskeletal matrix, was enhanced in CD151-overexpressing cells. Levels of GTP-bound Cdc42 and Rac were also elevated in CD151-overexpressing cells, suggesting the role of CD151 in E-cadherin-mediated cell-cell adhesion as a modulator of actin cytoskeletal reorganization. Consistent with this possibility, engagement of CD151 by the substrate-adsorbed anti-CD151 mAb induced prominent Cdc42-dependent filopodial extension, which along with E-cadherin puncta formation, was strongly inhibited by calphostin C, a protein kinase C (PKC) inhibitor. Together, these results indicate that CD151 is involved in epithelial cell-cell adhesion as a modulator of PKC- and Cdc42-dependent actin cytoskeletal reorganization.
Shigeta
Masaki
M
Institute for Protein Research, Osaka University, 3-2 Yamadaoka, Suita, Osaka 565-0871, Japan.
Sanzen
Noriko
N
Ozawa
Masayuki
M
Gu
Jianguo
J
Hasegawa
Hitoshi
H
Sekiguchi
Kiyotoshi
K
D000199:Actins / Q000378:metabolism; D015703:Antigens, CD / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism; D002448:Cell Adhesion / Q000502:physiology; D003599:Cytoskeleton / Q000378:metabolism*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D011493:Protein Kinase C / Q000378:metabolism*; D011554:Pseudopodia; D060185:Tetraspanin 24; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism*
D000199:Actins; D015703:Antigens, CD; C554715:CD151 protein, human; D015820:Cadherins; D060185:Tetraspanin 24; D011493:Protein Kinase C; D020764:cdc42 GTP-Binding Protein