The intracellular domain of major histocompatibility class-I proteins is essential for maintaining excitatory spine density and synaptic ultrastructure in the brain.

Autor: Lazarczyk MJ; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Department of Medical Direction and Quality, Division of Institutional Measures, University Hospitals of Geneva, Geneva, Switzerland., Eyford BA; Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.; The Vancouver Prostate Centre, Robert H.N. Ho Research Centre, Vancouver General Hospital, 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, Canada., Varghese M; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Arora H; Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.; The Vancouver Prostate Centre, Robert H.N. Ho Research Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.; Department of Microbiology and Immunology, University of British Columbia, 1365 - 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada., Munro L; Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.; The Vancouver Prostate Centre, Robert H.N. Ho Research Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.; Department of Microbiology and Immunology, University of British Columbia, 1365 - 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.; Centre for Blood Research, University of British Columbia, 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, Life Sciences Institute, 1364 - 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, Canada., Warda T; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Pfeifer CG; Michael Smith Laboratories, The University of British Columbia, 2185 East Mall, Vancouver, BC, V6T 1Z4, Canada.; The Vancouver Prostate Centre, Robert H.N. Ho Research Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6H 3Z6, Canada.; Department of Microbiology and Immunology, University of British Columbia, 1365 - 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.; Centre for Blood Research, University of British Columbia, 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, Life Sciences Institute, 1364 - 2350 Health Sciences Mall, Vancouver, BC, V6T 1Z3, Canada.; Djavad Mowafaghian Centre for Brain Health, University of British Columbia, 2215 Wesbrook Mall, Vancouver, BC, Canada., Sowa A; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Dickstein DR; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., Rumbell T; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA., 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, Robert H.N. Ho Research Centre, Vancouver General Hospital, 2660 Oak Street, Vancouver, BC, V6H 3Z6, 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.; Centre for Blood Research, University of British Columbia, 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, Life Sciences Institute, 1364 - 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, Canada. wilf@msl.ubc.ca., Dickstein DL; Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. dara.dickstein@usuhs.edu.; Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA. dara.dickstein@usuhs.edu.; Department of Pathology, Uniformed Services University of the Health Sciences, 4301 Jones Bridge Rd, Bethesda, MD, 20814, USA. dara.dickstein@usuhs.edu.; The Henry M. Jackson Foundation for the Advancement of Military Medicine Inc., Bethesda, MD, 20817, USA. dara.dickstein@usuhs.edu.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Apr 20; Vol. 13 (1), pp. 6448. Date of Electronic Publication: 2023 Apr 20.
DOI: 10.1038/s41598-023-30054-8
Abstrakt: Major histocompatibility complex class I (MHC-I) proteins are expressed in neurons, where they regulate synaptic plasticity. However, the mechanisms by which MHC-I functions in the CNS remains unknown. Here we describe the first structural analysis of a MHC-I protein, to resolve underlying mechanisms that explains its function in the brain. We demonstrate that Y321F mutation of the conserved cytoplasmic tyrosine-based endocytosis motif YXXΦ in MHC-I affects spine density and synaptic structure without affecting neuronal complexity in the hippocampus, a region of the brain intimately involved in learning and memory. Furthermore, the impact of the Y321F substitution phenocopies MHC-I knock-out (null) animals, demonstrating that reverse, outside-in signalling events sensing the external environment is the major mechanism that conveys this information to the neuron and this has a previously undescribed yet essential role in the regulation of synaptic plasticity.
(© 2023. The Author(s).)
Databáze: MEDLINE
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