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Nat Neurosci. 2005 May;8(5):606-15. Epub 2005 Apr 17.

Asymmetric membrane ganglioside sialidase activity specifies axonal fate.

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  • 1Cavalieri Ottolenghi Scientific Institute, University of Turin, 10043 Orbassano, Turin, Italy.

Abstract

Axon specification triggers the polarization of neurons and requires the localized destabilization of filamentous actin. Here we show that plasma membrane ganglioside sialidase (PMGS) asymmetrically accumulates at the tip of one neurite of the unpolarized rat neuron, inducing actin instability. Suppressing PMGS activity blocks axonal generation, whereas stimulating it accelerates the formation of a single (not several) axon. PMGS induces axon specification by enhancing TrkA activity locally, which triggers phosphatidylinositol-3-kinase (PI3K)- and Rac1-dependent inhibition of RhoA signaling and the consequent actin depolymerization in one neurite only. Thus, spatial restriction of an actin-regulating molecular machinery, in this case a membrane enzymatic activity, before polarization is enough to determine axonal fate.

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PMID:
15834419
[PubMed - indexed for MEDLINE]
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