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Semaphorin 3A inhibits ERM protein phosphorylation in growth cone filopodia through inactivation of PI3K
Author(s) -
Gallo Gianluca
Publication year - 2008
Publication title -
developmental neurobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.716
H-Index - 129
eISSN - 1932-846X
pISSN - 1932-8451
DOI - 10.1002/dneu.20631
Subject(s) - filopodia , growth cone , phosphorylation , microbiology and biotechnology , semaphorin , biology , ezrin , sema3a , actin cytoskeleton , moesin , actin , cytoskeleton , biochemistry , receptor , cell , axon
Ezrin–radixin–moesin (ERM) proteins are involved in the linkage of membranes to theactin filament (F‐actin) cytoskeleton. Phosphorylation of the C‐terminus activates the F‐actin binding domain of ERM proteins by preventing the action of an autoinhibitory domain. In this study, we investigated whether a growth cone collapsing signal, semaphorin 3A (Sema3A), alters the state of ERM C‐terminus phosphorylation. In the growth cones of dorsal root ganglion axons, phosphorylated ERM proteins localize to filopodia. We report that Sema3A inhibits ERM protein phosphorylation in growth cone filopodia. Significantly, Sema3A decreased ERM phosphorylation prior to the onset of growth cone collapse. Over‐expression of the F‐actin binding fragment of ERM proteins, which competes with endogenous ERM proteins for binding to F‐actin, inhibited filopodial initiation and dynamics. Sema3A has been previously shown to inhibit phosphoinositide 3‐kinase (PI3K) activity. Inhibition of PI3K resulted in the loss of phosphorylated ERM proteins from growth cone filopodia, and treatment with a PI3K activating peptide blocked the effects of Sema3A on ERM phosphorylation. Collectively, these observations demonstrate that inactivation of PI3K in response to Sema3A results in decreased phosphorylation of ERM proteins in filopodia thereby contributing to growth cone collapse. © 2008 Wiley Periodicals, Inc. Develop Neurobiol, 2008.