INSTITUTO DE INVESTIGACIONES BIOTECNOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
In silico characterization and functional analysis of non - synonymous polymorphisms (nsSNPs) present in GPM6 A ?s extracellular coding regions
LIC. GABRIELA INÉS APARICIO; DR. ALBERTO C. C. FRASCH; LIC. ANTONELA LEÓN; DRA. CAMILA SCORTICATI
Congreso; XXXIV Reunión Anual SAN 2019; 2019
Sociedad Argentina de Investigación en Neurociencias
Neuronal membrane glycoprotein M6a promotes neurite and axonal outgrowth, filopodia/spines formation and synaptogenesis in neuronal cultures. Altered expression or single nucleotide polymorphisms (SNPs) in GPM6A are associated with neurological disorders such as schizophrenia, depression, claustrophobia and Alzheimer?s disease. However, the molecular mechanisms underlying the development of such pathologies remain unknown. M6a shares topology with the tetraspanin family, containing: four transmembrane domains, two extracellular loops (EC1 and EC2), an intracellular loop and the N- and C-regions facing the cell cytoplasm. Interestingly, tetraspanin?s extracellular loops are crucial for specific and functional protein-protein interactions. Accordingly, we speculate that certain amino acids within M6a?s extracellular loops mediate specific interactions thus contributing to its function. We selected 13 non-synonymous SNPs located at GPM6A extracellular regions from the dbSNP database. In silico analysis predicted that all nsSNPs decrease protein stability and/or have potential functional effect. Indeed, functional analysis showed that one SNP located in EC1 (T71P) and four in EC2 (M154V, F156Y, R163Q and T210N) impaired M6a-induced neurite extension and/or filopodia in neurons. In conclusion, we provide evidence of the critical role of certain residues located on EC1 and EC2 on M6a function and the potential risk of these nsSNPs.