title: PKCdelta and cofilin activation affects peripheral actin reorganization and cell-cell contact in cells expressing integrin alpha5 but not its tailless mutant.
abstract: Integrin-mediated cell adhesion transduces signaling activities for actin reorganization, which is crucially involved in cellular function and architectural integrity. In this study, we explored the possibility of whether cell-cell contacts might be regulated via integrin-alpha5beta1-mediated actin reorganization. Ectopic expression of integrin alpha5 in integrin-alpha5-null intestinal epithelial cells resulted in facilitated retraction, cell-cell contact loss, and wound healing depending on Src and PI3K (phosphoinositide 3-kinase) activities by a reagent that affects actin organization. However, cytoplasmic tailless integrin alpha5 (hereafter referred to as alpha5/1) expression caused no such effects but rather sustained peripheral actin fibers, regardless of Src and PI3K signaling activities. Furthermore, integrin alpha5 engagement with fibronectin phosphorylated Ser643 of PKCdelta, upstream of FAK and Src and at a transmodulatory loop with PI3K/Akt. Pharmacological PKCdelta inactivation, dominant-negative PKCdelta adenovirus or inactive cofilin phosphatase (SSH1L mutant) retrovirus infection of alpha5-expressing cells sustained peripheral actin organization and blocked the actin reorganizing-mediated loss of cell-cell contacts. Meanwhile, wild-type PKCdelta expression sensitized alpha5/1-expressing cells to the actin disruptor to induce cell scattering. Altogether, these observations indicate that integrin alpha5, but not alpha5/1, mediates PKCdelta phosphorylation and cofilin dephosphorylation, which in turn modulate peripheral actin organization presumably leading to an efficient regulation of cell-cell contact and migration.
authors.affiliation: Cancer Research Institute, College of Medicine, Seoul National University, 28, Yeongeon-dong, Jongno-gu, Seoul 110-799, Korea.
authors.forename: Min-A
authors.initials: MA
authors.lastname: Oh
authors.forename: Eun-Sil
authors.initials: ES
authors.lastname: Kang
authors.forename: Sin-Ae
authors.initials: SA
authors.lastname: Lee
authors.forename: Eun-Ok
authors.initials: EO
authors.lastname: Lee
authors.forename: Yong-Bae
authors.initials: YB
authors.lastname: Kim
authors.forename: Sung-Hoon
authors.initials: SH
authors.lastname: Kim
authors.forename: Jung Weon
authors.initials: JW
authors.lastname: Lee
mesh_terms: D051339:Actin Depolymerizing Factors / Q000302:isolation & purification / Q000378:metabolism*; D000199:Actins / Q000302:isolation & purification / Q000378:metabolism*; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000378:metabolism; D006801:Humans; D039482:Integrin alpha5 / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000302:isolation & purification / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D010750:Phosphoproteins / Q000302:isolation & purification / Q000378:metabolism; D010766:Phosphorylation; D051745:Protein Kinase C-delta / Q000378:metabolism*; D051381:Rats; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000302:isolation & purification / Q000378:metabolism
chemical_list: D051339:Actin Depolymerizing Factors; D000199:Actins; D039482:Integrin alpha5; D008565:Membrane Proteins; D050505:Mutant Proteins; D010750:Phosphoproteins; C569042:TJP1 protein, human; C569044:Tjp1 protein, rat; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D019869:Phosphatidylinositol 3-Kinases; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051745:Protein Kinase C-delta