SAN2020

The molecular mechanisms underlying structural neuronal plasticity are not completely understood. In this regard, neuronal membrane glycoprotein M6a contributes to this process by unknown mechanisms. Alterations in M6a levels are associated with mental disorders like schizophrenia, depression and Alzheimer’s disease. Evidence suggests that the extracellular loops of M6a command its neuroplastic function. Therefore, we aimed to identify proteins that associate with M6a’s extracellular loops. We generated a chimera protein that only contains the extracellular loops of M6a and performed a co-immunoprecipitation with rat hippocampus samples followed by TMT/MS identification. Data analysis revealed 72 candidate proteins to interact with M6a’s extracellular loops. Gene ontology analysis showed that 45 of these proteins are located at the synapses while 22 are in the surface of oligodendrocytes. We characterized the interaction of M6a with piccolo, SV2B, and synapsin 1 in cultured hippocampal neurons. Moreover, we demonstrated the interaction between M6a with proteolipid protein (PLP) in N2a cells. Finally, a disease-associated genes and variants screening by DisGeNET revealed that most of the 72 proteins are involved in “autistic disorder,” “epilepsy,” and “seizures” increasing the spectrum of disorders in which M6a could play a role. Data are available via ProteomeXchange with identifier PXD017347.