Outside-in signaling through the major histocompatibility complex class-I cytoplasmic tail modulates glutamate receptor expression in neurons

Autor: 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
Jazyk: angličtina
Rok vydání: 2023
Předmět:
Zdroj: Scientific Reports, Vol 13, Iss 1, Pp 1-10 (2023)
Druh dokumentu: article
ISSN: 2045-2322
DOI: 10.1038/s41598-023-38663-z
Popis: 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.
Databáze: Directory of Open Access Journals
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