The intracellular domain of major histocompatibility class-I proteins is essential for maintaining excitatory spine density and synaptic ultrastructure in the brain
In: Scientific Reports, Jg. 13 (2023-04-20)
Online
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Zugriff:
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.
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The intracellular domain of major histocompatibility class-I proteins is essential for maintaining excitatory spine density and synaptic ultrastructure in the brain
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Autor/in / Beteiligte Person: | Lazarczyk, Maciej J. ; Eyford, Brett A. ; Varghese, Merina ; Arora, Hitesh ; Munro, Lonna ; Warda, Tahia ; Pfeifer, Cheryl G. ; Sowa, Allison ; Dickstein, Daniel R. ; Rumbell, Timothy ; Jefferies, Wilfred A. ; Dickstein, Dara L. |
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Zeitschrift: | Scientific Reports, Jg. 13 (2023-04-20) |
Veröffentlichung: | Springer Science and Business Media LLC, 2023 |
Medientyp: | unknown |
ISSN: | 2045-2322 (print) |
DOI: | 10.1038/s41598-023-30054-8 |
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