Involvement of protein phosphatase 2A in the maintenance of E-cadherin-mediated cell-cell adhesion through recruitment of IQGAP1.
Serine/threonine protein phosphatase (PP) 2A regulates many biological processes, however it remains unclear whether PP2A participates in cadherin-mediated cell-cell adhesion. We show here that the core enzyme of PP2A (PP2A-AC) is localized in the cell-cell adhesion sites between adjacent cells and associated with the E-cadherin-catenins complex in non-malignant human mammary epithelial (HME) cells at confluence. Treatment of the cells with either okadaic acid (OA), an inhibitor of PP2A, or siRNA for the regulatory subunit A of PP2A (PP2A-A) caused disruption of cell-cell adhesion and F-actin assembly, without affecting the complex formation of E-cadherin with beta- and alpha-catenins. While a small GTPase Rac and its effector IQGAP1 were associated with the E-cadherin-catenins complex, either OA or PP2A-A siRNA concomitantly induced the dissociation of IQGAP1, but not Rac, from the complex and the internalization of E-cadherin from the cell surface. We therefore propose that PP2A plays a crucial role in the maintenance of cell-cell adhesion through recruitment of IQGAP1 to the Rac-bound E-cadherin-catenins complex.
Takahashi
Kazuhide
K
Molecular Cell Biology Division, Kanagawa Cancer Center Research Institute, Yokohama, Japan. ktaka@gancen.asahi.yokohama.jp
Nakajima
Eri
E
Suzuki
Katsuo
K
D000199:Actins / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism*; D051177:Catenins / Q000378:metabolism; D002448:Cell Adhesion; D002460:Cell Line; D006801:Humans; D042361:Mammary Glands, Human / Q000166:cytology; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism / Q000502:physiology*; D011485:Protein Binding / Q000502:physiology; D054648:Protein Phosphatase 2; D034622:RNA Interference; D034741:RNA, Small Interfering; D020703:ras GTPase-Activating Proteins / Q000378:metabolism* / Q000502:physiology
D000199:Actins; D015820:Cadherins; D051177:Catenins; C101203:IQ motif containing GTPase activating protein 1; D034741:RNA, Small Interfering; D020703:ras GTPase-Activating Proteins; D019319:Okadaic Acid; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2