MHCI promotes developmental synapse elimination and aging-related synapse loss at the vertebrate neuromuscular junction

Brain, Behavior, and Immunity
Mazell M TetruashvilyLisa M Boulanger

Abstract

Synapse elimination at the developing neuromuscular junction (NMJ) sculpts motor circuits, and synapse loss at the aging NMJ drives motor impairments that are a major cause of loss of independence in the elderly. Here we provide evidence that at the NMJ, both developmental synapse elimination and aging-related synapse loss are promoted by specific immune proteins, members of the major histocompatibility complex class I (MHCI). MHCI is expressed at the developing NMJ, and three different methods of reducing MHCI function all disrupt synapse elimination during the second postnatal week, leaving some muscle fibers multiply-innervated, despite otherwise outwardly normal synapse formation and maturation. Conversely, overexpressing MHCI modestly accelerates developmental synapse elimination. MHCI levels at the NMJ rise with aging, and reducing MHCI levels ameliorates muscle denervation in aged mice. These findings identify an unexpected role for MHCI in the elimination of neuromuscular synapses during development, and indicate that reducing MHCI levels can preserve youthful innervation of aging muscle.

Citations

May 12, 2017·EMBO Molecular Medicine·Sadanori MiyoshiYuji Yamanashi
Sep 6, 2020·Current Opinion in Rheumatology·Marta Loredo MartinezMariele Gatto
Mar 7, 2020·Cell Discovery·Xiu-Qing FuZhen-Ge Luo
Dec 2, 2017·Annual Review of Physiology·Lei LiLin Mei
Nov 26, 2019·Experimental Gerontology·Xianyi LinXin Yu
Dec 22, 2020·Frontiers in Molecular Neuroscience·Pedro M Rodríguez CruzAngela Vincent
Mar 4, 2021·Cell Discovery·Xiu-Qing FuZhen-Ge Luo

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