Evidence for a Role of Glycoprotein M6a in Dendritic Spine Formation and Synaptogenesis

FORMOSO, K; GARCIA, M; ALBERTO CC FRASCH; CAMILA SCORTICATI

MOLECULAR AND CELLULAR NEUROSCIENCES.

ACADEMIC PRESS INC ELSEVIER SCIENCE

Lugar: Amsterdam; Año: 2016 vol. 77 p. 97 - 104

1044-7431

Neuronal glycoprotein M6a belongs to the tetraspan proteolipidprotein (PLP) family. Mutations in GPM6A gene have been related to mentaldisorders like schizophrenia, bipolar disorders and claustrophobia. M6ais expressed mainly in neuronal cells of the central nervous system andit has been extensively related to neuronal plasticity. M6a inducesneuritogenesis and axon/filopodium outgrowth; however its mechanism ofaction is still unresolved. We recently reported that the integrity ofthe transmembrane domains (TMDs) 2 and 4 are critical for M6a filopodiainduction. There is also experimental data suggesting that M6a might beinvolved in synaptogenesis. In this regard, we have previously determinedthat M6a is involved in filopodia motility, a process that is describedin the first step of the filopodial model for synaptogenesis. In thiswork we analyzed the possible involvement of M6a in synaptogenesis andspinogenesis, and evaluated the effect of two non-synonymous SNPs presentin the coding region of TMD2-GPM6A in these processes. The results showedthat endogenous M6a colocalized with both, pre-synaptic (synaptophysin)and post-synaptic (NMDA-R1), markers along of neuronal soma anddendrites. M6a-overexpressing neurons displayed an increased number ofsynaptophysin and NMDA-R1 puncta and, also, an increased number ofcolocalization puncta between both markers. Conversely, the number ofsynaptic puncta markers in neurons expressing nsSNP variants was similarto those of control neurons. Expression of M6a is accompanied by anincrement in spine density, particularly in mature spines, as comparedwith neurons expressing mGFP or GPM6A nsSNP variants. Taken together,these results suggest that M6a contributes positively to spine and,likely, synapse formation