The SNAREs SNAP23, VAMP4 and Syntaxin6 are necessary for the establishment of neuronal polarity

BUSTOS PLONKA, F.; GRASSI, D.; QUIROGA, S.

Mar del Plata

Exposición; XXX Congreso de la Sociedad Argentina de Investigaciones en Neurociencias (SAN); 2015

Theestablishment of neuronal polarity necessitates the addition of new membrane tothe axon?s plasmalemma. Axolemmal expansion occurs by exocytosis ofplasmalemmal precursor vesicles (PPVs) primarily at the axonal growth cone.Previous published data from our laboratory indicates that, in culturedhippocampal neurons, TC10 activation by IGF-1 and recruitment of exo70 to thegrowth cone plasmalemma are necessary for the regulation of PPVs exocytosis. Incontrast, little is known about the SNARE proteins involved in the regulationof PPV fusion with the neuronal plasmalemma at early stages of differentiation.We show here that VAMP2, VAMP4, VAMP7, Syntaxin6 and SNAP23 are expressed byhippocampal pyramidal neurons before polarization. Expression silencing ofVAMP4, Syntaxin6 and SNAP23 repressed axonal outgrowth and the establishment ofneuronal polarity, by inhibiting IGF-1 receptor exocytotic polarized insertion.In addition, stimulation with IGF-1 triggered the association of VAMP4,Syntaxin6 and SNAP23 to vesicular structures carrying the IGF-1 receptor andover-expression of a negative dominant form of Syntaxin6 significantlyinhibited exocytosis of IGF-1 receptor containing vesicles at the neuronalgrowth cone. Taken together, our results indicated that VAMP4, Syntaxin6 andSNAP23 function are essential for regulation of PPVs exocytosis and thepolarized insertion of IGF-1 receptor and required for initial axonalelongation and the establishment of neuronal polarity.