Site-directed MT1-MMP trafficking and surface insertion regulate achr clustering and remodeling at developing NMJS

Zora Chui Kuen Chan, Hiu Lam Rachel Kwan, Yin Shun Wong, Zhixin Jiang, Zhongjun Zhou, Kin Wai Tam, Ying Shing Chan, Chi Bun Chan, Chi Wai Lee*

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

19 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere54379
Number of pages33
JournaleLife
Volume9
DOIs
Publication statusPublished - 24 Mar 2020

Scopus Subject Areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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