Session: 3

PS3-17 | nsSNPs within the extracellular loops of M6a impair its neuroplastic function

Antonella León

Instituto de Investigaciones Biotecnológicas (IIBio)

The expression levels or polymorphisms within the GPM6A gene are associated with neuropsychiatric disorders such as schizophrenia, depression and claustrophobia. GPM6A encodes the neuronal membrane glycoprotein M6a, which promotes filopodia/spine and synapse formation in vitro. Even though strong evidence suggests that the extracellular loops of M6a (ECs) command its function, the molecular mechanisms linking M6a to the onset of such diseases remain unknown. To gain knowledge on this mechanisms, we aim to characterize new non-synonymous polymorphisms (nsSNPs) in the coding region of ECs of GPM6A. Preliminary results suggest that the mutants expression, subcellular localization and folding are not affected by the presence of nsSNPs. However, we identified nsSNPs that impaired M6a-induced plasticity in neuronal cultures and now we are focusing on the mechanisms by which the protein’s function fails. In this sense, previous reports showed that M6a dimerization is necessary to induce filopodia and synapse formation. M6a´s ECs are involved in homo- and heterotypic protein-protein interactions and might lead to the formation of M6a oligomers at the plasma membrane. Thus, we are currently evaluating whether the nsSNPs might disturb the protein’s oligomerization through number and brightness analysis (N&B), which allows us to monitor RFP-tagged M6a oligomer distribution in live cells.