Changes in alternative splicing of GluN1 NMDAR subunit in a GluN2A-NMDAR KD model

GOBBINI, MARIA LAURA; ACUTAIN, MARIA FLORENCIA; CANAL, MARIA PILAR; BAEZ, MARÍA VERÓNICA

virtual

Congreso; XXXV Annual Meeting of the Argentinian Society for Neuroscience Research; 2020

Sociedad Argentina de Neurociencia

NMDAR receptor (NMDAR)is a heterotetramer composed of two obligatory subunits, GluN1; and tworegulatory subunits, GluN2 (A to D) or GluN3 (A and B). Alternative splicing of GluN1 mRNA produces eightsplice variants that alternate in, N1 cassette at the N terminal or, concerningthe C-terminal,  GluN1 variants are due tothe presence or absence of C1, C2 and C2? cassettes. Previous works have described that knock-down(KD) of GluN2A regulatory subunit produces alterations in expression of GluN1. Inthis work, we analyse if changes in GluN1 expression in GluN2A KD are relatedto changes in NDMAR subcellular localization and also, if these changes areassociated to modifications in NMDAR splicing variants. Preliminary results showedthat N1 cassette inclusion does not change due to GluN2A KD, nonetheless, wefound changes in the alternative splicing of C-terminus cassettes. Furthermore,we observed changes in GluN1 levels both at soma and dendrites. Although these arepreliminary results, they suggest that changes in GluN2A modulate the NMDARlocalization and the alternative splicing of GluN1.