Differential roles of PtdIns(4,5)P2 and phosphorylation in moesin activation during Drosophila development.
The ezrin, radixin and moesin (ERM) proteins regulate cell membrane architecture in several cellular contexts. Current models propose that ERM activation requires a PtdIns(4,5)P(2)-induced conformational change, followed by phosphorylation of a conserved threonine. However, how these inputs contribute in vivo to orchestrate ERM activation is poorly understood. We addressed this issue by evaluating the contribution of PtdIns(4,5)P(2) and phosphorylation to the regulation of moesin during Drosophila development. Unexpectedly, we found that a form of moesin that cannot be phosphorylated displayed significant activity and could substitute for the endogenous product during wing morphogenesis. By contrast, we also show that PtdIns(4,5)P(2) binding is essential for moesin recruitment to the membrane and for its subsequent phosphorylation. Our data indicate that PtdIns(4,5)P(2) acts as a dosing mechanism that locally regulates ERM membrane recruitment and activation, whereas cycles of phosphorylation and dephosphorylation further control their activity once they have reached the cell cortex.
Roch
Fernando
F
Université de Toulouse UPS, Centre de Biologie du Développement, Toulouse, France. roch@cict.fr
Polesello
Cédric
C
Roubinet
Chantal
C
Martin
Marianne
M
Roy
Christian
C
Valenti
Philippe
P
Carreno
Sébastien
S
Mangeat
Paul
P
Payre
François
F
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D004330:Drosophila / Q000737:chemistry / Q000235:genetics / Q000254:growth & development* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008840:Microfilament Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D010766:Phosphorylation; D011485:Protein Binding; D021381:Protein Transport; D016415:Sequence Alignment; D014921:Wings, Animal / Q000737:chemistry / Q000254:growth & development / Q000378:metabolism; D000099149:Ezrin
D003598:Cytoskeletal Proteins; D029721:Drosophila Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D000099149:Ezrin; C071058:moesin; C071776:radixin