Asymmetric membrane ganglioside sialidase activity specifies axonal fate.
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.
Da Silva
Jorge Santos
JS
Cavalieri Ottolenghi Scientific Institute, University of Turin, 10043 Orbassano, Turin, Italy.
Hasegawa
Takafumi
T
Miyagi
Taeko
T
Dotti
Carlos G
CG
Abad-Rodriguez
Jose
J
D000199:Actins / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D016764:Cell Polarity / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020439:Growth Cones / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D020917:Receptor, trkA / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D000199:Actins; D004791:Enzyme Inhibitors; D019869:Phosphatidylinositol 3-Kinases; D020917:Receptor, trkA; C465436:Neu3 protein, human; D009439:Neuraminidase; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein