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Elife January 1, 2020; 9

Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs.

Chan ZC , Kwan HR , Wong YS , Jiang Z , Zhou Z , Tam KW , Chan YS , Chan CB , Lee CW .

At vertebrate neuromuscular junctions (NMJs), the synaptic basal lamina contains different extracellular matrix (ECM) proteins and synaptogenic factors that induce and maintain synaptic specializations. Here, we report that podosome-like structures (PLSs) induced by ubiquitous ECM proteins regulate the formation and remodeling of acetylcholine receptor (AChR) clusters via focal ECM degradation. Mechanistically, ECM degradation is mediated by PLS-directed trafficking and surface insertion of membrane-type 1 matrix metalloproteinase (MT1-MMP) to AChR clusters through microtubule-capturing mechanisms. Upon synaptic induction, MT1-MMP plays a crucial role in the recruitment of aneural AChR clusters for the assembly of postsynaptic specializations. Lastly, the structural defects of NMJs in embryonic MT1-MMP-/- mice further demonstrate the physiological role of MT1-MMP in normal NMJ development. Collectively, this study suggests that postsynaptic MT1-MMP serves as a molecular switch to synaptogenesis by modulating local ECM environment for the deposition of synaptogenic signals that regulate postsynaptic differentiation at developing NMJs.

PubMed ID: 32208136
PMC ID: PMC7093154
Article link: Elife
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: aagab cox7a2l cttn endoul mapre1 mt4 mtnr1a mtor pxn
GO keywords: neuromuscular junction

Article Images: [+] show captions
References [+] :
Anderson, Nerve-induced and spontaneous redistribution of acetylcholine receptors on cultured muscle cells. 1977, Pubmed, Xenbase