Premium
Regulation of actomyosin contractility by PI3K in sensory axons
Author(s) -
Orlova Irina,
Silver Lee,
Gallo Gianluca
Publication year - 2007
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.20558
Subject(s) - growth cone , semaphorin , biology , microbiology and biotechnology , axon , actin cytoskeleton , filopodia , pi3k/akt/mtor pathway , myosin , neuroscience , actin remodeling , actin , cytoskeleton , rhoa , signal transduction , biochemistry , receptor , cell
Phosphatidylinositol 3‐kinase (PI3K) activity is known to be required for the extension of embryonic sensory axons. Inhibition of PI3K has also been shown to mediate axon retraction and growth cone collapse in response to semaphorin 3A. However, the effects of inhibiting PI3K on the neuronal cytoskeleton are not well characterized. We have previously reported that semaphorin 3A‐induced axon retraction involves activation of myosin II, the formation of an intra‐axonal F‐actin bundle cytoskeleton, and blocks the formation of F‐actin patches that serve as precursors to filopodial formation in axons. We now report that inhibition of PI3K results in activation of myosin II in axons. Inhibition of myosin II activity, or its upstream regulatory kinase RhoA‐kinase, blocked axon retraction induced by inhibition of PI3K. In addition, inhibition of PI3K also induced intra‐axonal F‐actin bundles, which likely serve as a substratum for myosin II‐based force generation during axon retraction. In axons, filopodia are formed from axonal F‐actin patch precursors. Analysis of axonal F‐actin patch formation in eYFP‐actin expressing neurons revealed that inhibition of PI3K blocked formation of axonal F‐actin patches, and thus filopodial formation. These data provide insights into the regulation of the neuronal cytoskeleton by PI3K and are consistent with the notion that decreased levels of PI3K activity mediate axon retraction and growth cone collapse in response to semaphorin 3A. © 2007 Wiley Periodicals, Inc. Develop Neurobiol, 2007.