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

TitleSite-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs
Authors
Issue Date2020
PublishereLife Sciences Publications Ltd. The Journal's web site is located at http://elifesciences.org/
Citation
eLife, 2020, v. 9, article no. e54379 How to Cite?
AbstractAt 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.
Persistent Identifierhttp://hdl.handle.net/10722/281776
ISSN
2019 Impact Factor: 7.08
2015 SCImago Journal Rankings: 6.356
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorChan, ZCK-
dc.contributor.authorKwan, HLR-
dc.contributor.authorWong, YS-
dc.contributor.authorJiang, Z-
dc.contributor.authorZhou, Z-
dc.contributor.authorTam, KW-
dc.contributor.authorChan, YS-
dc.contributor.authorChan, CB-
dc.contributor.authorLee, CW-
dc.date.accessioned2020-03-27T04:22:24Z-
dc.date.available2020-03-27T04:22:24Z-
dc.date.issued2020-
dc.identifier.citationeLife, 2020, v. 9, article no. e54379-
dc.identifier.issn2050-084X-
dc.identifier.urihttp://hdl.handle.net/10722/281776-
dc.description.abstractAt 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.-
dc.languageeng-
dc.publishereLife Sciences Publications Ltd. The Journal's web site is located at http://elifesciences.org/-
dc.relation.ispartofeLife-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleSite-directed MT1-MMP trafficking and surface insertion regulate AChR clustering and remodeling at developing NMJs-
dc.typeArticle-
dc.identifier.emailZhou, Z: zhongjun@hku.hk-
dc.identifier.emailTam, KW: tamkw@hku.hk-
dc.identifier.emailChan, YS: yschan@hku.hk-
dc.identifier.emailChan, CB: chancb@hku.hk-
dc.identifier.emailLee, CW: chiwai.lee@hku.hk-
dc.identifier.authorityZhou, Z=rp00503-
dc.identifier.authorityChan, YS=rp00318-
dc.identifier.authorityChan, CB=rp02140-
dc.identifier.authorityLee, CW=rp02089-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.7554/eLife.54379-
dc.identifier.pmid32208136-
dc.identifier.pmcidPMC7093154-
dc.identifier.scopuseid_2-s2.0-85081756791-
dc.identifier.hkuros309558-
dc.identifier.volume9-
dc.identifier.spagearticle no. e54379-
dc.identifier.epagearticle no. e54379-
dc.identifier.isiWOS:000521946900001-
dc.publisher.placeCambridge, UK-
dc.identifier.issnl2050-084X-

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