Transmembrane domain self-interaction of neuronal membrane glycoprotein, M6a

KARINA FORMOSO; CAMILA SCORTICATI; ALBERTO C C FRASCH

Puerto Madryn

Congreso; SAIB; 2010

Sociedad argentina de Bioquímica y biología molecular

GPM6A is a stress/antidepressant-responsive gene expressed mainly in neurons of the hippocampus and it is believed to be involved in human depression. This gene is down regulated in both physically and socially stressed animals. M6a is a protein with four transmembrane domains (TMs), two extracellular loops and N- and C- terminal extensions toward the cell cytoplasm. M6a regulates neurite/filopodium outgrowth through an unknown mechanism. It is well known that self-association of membrane proteins is important in the regulation of extra and intracellular signaling pathways. Establishing a possible M6a-homologous interaction in rat hippocampus could give us a clue of how this protein exerts its function. In order to test the possibility that the M6a-TMs may be able to associate with itself we employed the TOXCAT system, which allows to monitor and asses TM-TM interactions in biological membranes. Additionally, to determine if M6a is organized as a monomer or an oligomer chemical crosslinking assays in rat hippocampus homogenate and cell lines were performed. The TOXCAT assay showed that there is self-interaction among all M6a transmembrane domains. Moreover, we found that endogenous M6a shows different oligomerization states. In conclusion, our data suggests that self-association of M6a-TMs could be involved in oligomers formation.