Inhibition of cell adhesion by phosphorylated Ezrin/Radixin/Moesin

• Published in: Cell adhesion & migration Vol. 9; no. 6; pp. 502 - 512
• Main Authors: Tachibana, Kouichi, Haghparast, Seyed Mohammad Ali, Miyake, Jun
• Format: Journal Article
• Language: English
• Published: United States Taylor & Francis 02.11.2015
• Subjects: cell adhesion; Cell Adhesion - genetics; Cell Line; Cell Membrane - metabolism; cell rounding; Cell Shape - genetics; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - metabolism; Cytoskeleton - metabolism; dephosphorylation; ERM; Humans; Membrane Proteins - genetics; Membrane Proteins - metabolism; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Oxazoles - administration & dosage; phosphorylation; Phosphorylation - drug effects; Research Paper; rigidity; spherical cell shape; ERM; spherical cell shape; cell adhesion; cell rounding; dephosphorylation; phosphorylation; rigidity
• ISSN: 1933-6918; 1933-6926
• DOI: 10.1080/19336918.2015.1113366

Altered phosphorylation status of the C-terminal Thr residues of Ezrin/Radixin/Moesin (ERM) is often linked to cell shape change. To determine the role of phophorylated ERM, we modified phosphorylation status of ERM and investigated changes in cell adhesion and morphology. Treatment with Calyculin-A (Cal-A), a protein phosphatase inhibitor, dramatically augmented phosphorylated ERM (phospho-ERM). Cal-A-treatment or expression of phospho-mimetic Moesin mutant (Moesin-TD) induced cell rounding in adherent cells. Moreover, reattachment of detached cells to substrate was inhibited by either treatment. Phospho-ERM, Moesin-TD and actin cytoskeleton were observed at the plasma membrane of such round cells. Augmented cell surface rigidity was also observed in both cases. Meanwhile, non-adherent KG-1 cells were rather rich in phospho-ERM. Treatment with Staurosporine, a protein kinase inhibitor that dephosphorylates phospho-ERM, up-regulated the integrin-dependent adhesion of KG-1 cells to substrate. These findings strongly suggest the followings: (1) Phospho-ERM inhibit cell adhesion, and therefore, dephosphorylation of ERM proteins is essential for cell adhesion. (2) Phospho-ERM induce formation and/or maintenance of spherical cell shape. (3) ERM are constitutively both phosphorylated and dephosphorylated in cultured adherent and non-adherent cells.