Role of lipid rafts in the neuronal plasticity mediated by M6a, a neuronal membrane glycoprotein

CAMILA SCORTICATI; FERNANDEZ, ME; FRASCH, AC.

San Miguel de Tucuman

Congreso; 45 th Annual Meeting Argentine Society for Biochemistry and Molecular Biology Research; 2009

SAIB

GPM6A is a stress/antidepressant-responsive gene in the hippocampus of different animal models.  This gene is down regulated in both physically and socially stressed animals. M6a regulates neurite/filopodium outgrowth in hippocampal neuronal culture through an unknown mechanism. The association of membrane proteins with specific microdomains such as lipid rafts (LP) in the plasma membrane is implicated in the regulation of extra and intracellular signaling pathways and would allow us to study M6a function. The goal of this work is to test if M6a carries out its cell functions in specialized membrane microdomains and if LP affects M6a pathway capacity. Using a discontinuous sucrose gradient followed by ultracentrifugation and SDS-PAGE-WB technique we identified the presence of M6a in the detergent resistant membrane fraction from both hippocampal tissue and cultured neurons. Next, by microscopy we determined M6a co-localization with gangliosides, a LP marker.  Futhermore, M6a overexpressing cultured neurons treated with MBCD (methyl-beta-cyclo-dextrin, a LP breaker) showed a drastically reduction in the number of filopodia/spines protrusion. Taken together, we showed that the association of M6a to lipid rafts membrane microdomains is involved in the neuronal fillopodium/spines formation.