Functional role of the duplicated alpha7 nicotinic receptor subunit

LASALA, M.; DIONISIO, L.; CORRADI, J.; CHRESTIA, F.; ESANDI, M.; BOUZAT, C.

Mar del Plata

Congreso; XXX Reunión Anual de la Sociedad Argentina de Investigación en Neurociencias (SAN); 2015

Sociedad Argentina de Investigación en Neurociencias (SAN)

The α7 nicotinic receptor subunit gene, CHRNA7,codes fora subunit that forms thehomomericα7 receptor, which is involved in learning and memory. Exons 5-10 of CHRNA7were duplicated upstreaminterrupting anotherpartial duplication of the gene ULK4, called FAM.The product of the resulting chimeric gene (CHRFAM7A), dupα7, is a receptor subunit that lacks part of the AChbinding site. We here combine cell expression and electrophysiological recordings in HEK cellsto understand the functional role of the dup7 subunit.Incorporation of dup7 cDNA during cell transfection with 7 cDNA reduces surface -BTX labeling, indicating reduced number of 7 binding sites, and in turn, suggesting a negative modulatory role. To determine if dup7 can assemble into functional receptors we used, as a reporter of receptor stoichiometry,an7 subunit(7LC) carrying mutations in determinants of ion conductance. 7LC forms functional receptors but single-channel openings cannot be detected due to their low conductance. Co-expression of 7LC with dup7, which by itself does not form functional receptors, allows detection of single-channel openingselicited by ACh. This result unequivocally indicates that α7 and dupα7 subunits assemble into functional heteromeric receptors. The analysisshowsthat a minimum of two 7 subunits is required for forming functional receptors. Our results contribute to the understanding of the functional significance of the partial duplication of the 7 gene.