| First Author | Chan ZC | Year | 2020 |
| Journal | Elife | Volume | 9 |
| PubMed ID | 32208136 | Mgi Jnum | J:290951 |
| Mgi Id | MGI:6442158 | Doi | 10.7554/eLife.54379 |
| Citation | Chan ZC, et al. (2020) Site-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs. Elife 9:e54379 |
| abstractText | 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. |
