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


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
11 08 2023
Historique:
received: 16 03 2023
accepted: 12 07 2023
medline: 14 8 2023
pubmed: 12 8 2023
entrez: 11 8 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37567897
doi: 10.1038/s41598-023-38663-z
pii: 10.1038/s41598-023-38663-z
pmc: PMC10421907
doi:

Substances chimiques

Glutamic Acid 3KX376GY7L
Receptors, Glutamate 0
Receptors, AMPA 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

13079

Subventions

Organisme : CIHR
ID : MOP-77631
Pays : Canada
Organisme : CIHR
ID : MOP-86739
Pays : Canada

Informations de copyright

© 2023. Springer Nature Limited.

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Auteurs

Brett A Eyford (BA)

Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.
The Vancouver Prostate Centre, Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.

Maciej J Lazarczyk (MJ)

Division of Institutional Measures, Department of Medical Direction and Quality, University Hospitals of Geneva, Geneva, Switzerland.
Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY, 10029, USA.

Kyung Bok Choi (KB)

Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.
The Vancouver Prostate Centre, Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Department of Zoology, University of British Columbia, 2370-6270 University Blvd., Vancouver, BC, V6T 1Z4, Canada.
Department of Medical Genetics, University of British Columbia, 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.

Merina Varghese (M)

Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY, 10029, USA.

Hitesh Arora (H)

Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.
The Vancouver Prostate Centre, Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.

Suresh Kari (S)

Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.
The Vancouver Prostate Centre, Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Department of Zoology, University of British Columbia, 2370-6270 University Blvd., Vancouver, BC, V6T 1Z4, Canada.
Department of Medical Genetics, University of British Columbia, 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.

Lonna Munro (L)

Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.
The Vancouver Prostate Centre, Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Department of Zoology, University of British Columbia, 2370-6270 University Blvd., Vancouver, BC, V6T 1Z4, Canada.
Department of Medical Genetics, University of British Columbia, 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.

Cheryl G Pfeifer (CG)

Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.
The Vancouver Prostate Centre, Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.
Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada.
Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.
Department of Zoology, University of British Columbia, 2370-6270 University Blvd., Vancouver, BC, V6T 1Z4, Canada.
Department of Medical Genetics, University of British Columbia, 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.

Allison Sowa (A)

Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY, 10029, USA.

Daniel R Dickstein (DR)

Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY, 10029, USA.

Dara L Dickstein (DL)

Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, 1425 Madison Ave, New York, NY, 10029, USA. dara.dickstein@usuhs.edu.
Department of Pathology, Uniformed Services University of Health Sciences, 4301 Jones Bridge Road, Bethesda, MD, 20814, USA. dara.dickstein@usuhs.edu.
The Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF), 6720A Rockledge Drive, Bethesda, MD, 20817, USA. dara.dickstein@usuhs.edu.

Wilfred A Jefferies (WA)

Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada. wilf@msl.ubc.ca.
The Vancouver Prostate Centre, Jack Bell Research Centre, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada. wilf@msl.ubc.ca.
Centre for Blood Research, University of British Columbia, 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. wilf@msl.ubc.ca.
Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, V6T 2B5, Canada. wilf@msl.ubc.ca.
Department of Microbiology and Immunology, University of British Columbia, 1365-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. wilf@msl.ubc.ca.
Department of Zoology, University of British Columbia, 2370-6270 University Blvd., Vancouver, BC, V6T 1Z4, Canada. wilf@msl.ubc.ca.
Department of Medical Genetics, University of British Columbia, 1364-2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada. wilf@msl.ubc.ca.

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