Outside-in Signaling Through the Major Histocompatibility Complex Class-I Cytoplasmic Tail Modulates Glutamate Receptor Expression in Neurons

Overview

Journal Sci Rep

Specialty Science

Date 2023 Aug 11

PMID 37567897

Authors

Brett A Eyford

Maciej J Lazarczyk

Kyung Bok Choi

Merina Varghese

Hitesh Arora

Suresh Kari

Lonna Munro

Cheryl G Pfeifer

Allison Sowa

Daniel R Dickstein

Dara L Dickstein

Wilfred A Jefferies

Affiliations

Soon will be listed here.

Abstract

The interplay between AMPA-type glutamate receptors (AMPARs) and major histocompatibility complex class I (MHC-I) proteins in regulating synaptic signaling is a crucial aspect of central nervous system (CNS) function. In this study, we investigate the significance of the cytoplasmic tail of MHC-I in synaptic signaling within the CNS and its impact on the modulation of synaptic glutamate receptor expression. Specifically, we focus on the Y321 to F substitution (Y321F) within the conserved cytoplasmic tyrosine YXXΦ motif, known for its dual role in endocytosis and cellular signaling of MHC-I. Our findings reveal that the Y321F substitution influences the expression of AMPAR subunits GluA2/3 and leads to alterations in the phosphorylation of key kinases, including Fyn, Lyn, p38, ERK1/2, JNK1/2/3, and p70 S6 kinase. These data illuminate the crucial role of MHC-I in AMPAR function and present a novel mechanism by which MHC-I integrates extracellular cues to modulate synaptic plasticity in neurons, which ultimately underpins learning and memory.

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