The Motor KIF5C Links the Requirements of Stable Microtubules and IGF-1 Receptor Membrane Insertion for Neuronal Polarization

QUIROGA, SANTIAGO

MOLECULAR NEUROBIOLOGY

HUMANA PRESS INC

Año: 2016 vol. 54 p. 6085 - 6085

0893-7648

hree early signals of asymmetry have been describedto occur in a single neurite of neurons at stage 2 ofdifferentiation (before polarization) and shown to be essentialfor neuronal polarization: (i) accumulation of stable microtubules,(ii) enrichment of the plasma membrane withactivatable IGF-1r, and (iii) polarized transport of the microtubularmotor KIF5C. Here, we studied the possible relationshipbetween these three phenomena. Our results show thatthe activatable (membrane-inserted) IGF-1r and stable microtubulesaccumulate in the same neurite of cells at stage 2. Thepolarized insertion of IGF-1r depends on microtubule dynamicsas shown using drugs which modify microtubule stability.Silencing of KIF5C expression prevents the polarized insertionof IGF-1r into the neuronal plasmalemma and neuronalpolarization. Syntaxin 6 and VAMP4, necessary for the polarizedinsertion of the IGF-1r, are associated to vesicles carriedby the microtubular motor KIF5C and is transported preferentiallyto the