8v14

Publication Abstract from PubMed

N-methyl-D-aspartate (NMDA)-type ionotropic glutamate receptors have essential roles in neurotransmission and synaptic plasticity. Previously, we identified an evolutionarily conserved protein, NRAP-1, that is required for NMDA receptor (NMDAR) function in C. elegans. Here, we demonstrate that NRAP-1 was sufficient to gate NMDARs and greatly enhanced glutamate-mediated NMDAR gating, thus conferring coincident activation properties to the NMDAR. Intriguingly, vertebrate NMDARs-and chimeric NMDARs where the amino-terminal domain (ATD) of C. elegans NMDARs was replaced by the ATD from vertebrate receptors-were spontaneously active when ectopically expressed in C. elegans neurons. Thus, the ATD is a primary determinant of NRAP-1- and glutamate-mediated gating of NMDARs. We determined the crystal structure of NRAP-1 at 1.9-A resolution, which revealed two distinct domains positioned around a central low-density lipoprotein receptor class A domain. The NRAP-1 structure, combined with chimeric and mutational analyses, suggests a model where the three NRAP-1 domains work cooperatively to modify the gating of NMDARs.

Mechanistic and structural studies reveal NRAP-1-dependent coincident activation of NMDARs.,Goodell DJ, Whitby FG, Mellem JE, Lei N, Brockie PJ, Maricq AJ, Eckert DM, Hill CP, Madsen DM, Maricq AV Cell Rep. 2024 Feb 27;43(2):113694. doi: 10.1016/j.celrep.2024.113694. Epub 2024 , Jan 23. PMID:38265937^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.