Neuronal glycoprotein M6a induces filopodia formation via association with cholesterol-rich lipid rafts

CAMILA SCORTICATI; FORMOSO, K; FRASCH, AC.

Florence

Congreso; 8 th IBRO 2011; 2011

International Brain Organization (IBRO)

Neuronal M6a, an integral membrane glycoprotein, has been suggested to be involved in a number of biological processes including neuronal remodeling and differentiation, trafficking of mu-opioid receptors and Ca transportation. Alterations in M6a sequence and expression have been associated with pathological situations such as chronic stress in animals and depression in humans. However, the mechanism of action of M6a is essentially unknown. In this work, we analyzed the relevance of M6a location on the membrane for its biological function, namely filopodia formation. M6a was found to be located in membrane microdomains compatible with lipid rafts in cultured rat hippocampal neurons. Removal of cholesterol from neuronal membranes with methyl-â-cyclodextrin decreased M6a-induced filopodia formation, an effect that was reversed by the addition of cholesterol. Inhibition of Src kinases and mitogen-activated protein kinase (MAPK) counteracted filopodia formation in M6a-overexpressing neurons. Src-deficient SYF cells overexpressing M6a failed to promote filopodia formation. These findings reveal that filopodia formation by M6a involves association with lipid rafts. Also, Src and MAPK kinases participate in M6a signal propagation.