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Arhgef5 Binds α-Dystrobrevin 1 and Regulates Neuromuscular Junction Integrity

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cris.lastimport.scopus2024-02-12T19:35:03Z
dc.abstract.enThe neuromuscular junctions (NMJs) connect muscle fibers with motor neurons and enable the coordinated contraction of skeletal muscles. The dystrophin-associated glycoprotein complex (DGC) is an essential component of the postsynaptic machinery of the NMJ and is important for the maintenance of NMJ structural integrity. To identify novel proteins that are important for NMJ organization, we performed a mass spectrometry-based screen for interactors of alpha-dystrobrevin 1 (aDB1), one of the components of the DGC. The guanidine nucleotide exchange factor (GEF) Arhgef5 was found to be one of the aDB1 binding partners that is recruited to Tyr-713 in a phospho-dependent manner. We show here that Arhgef5 localizes to the NMJ and that its genetic depletion in the muscle causes the fragmentation of the synapses in conditional knockout mice. Arhgef5 lossin vivois associated with a reduction in the levels of active GTP-bound RhoA and Cdc42 GTPases, highlighting the importance of actin dynamics regulation for the maintenance of NMJ integrity.
dc.affiliationUniwersytet Warszawski
dc.contributor.authorDaszczuk, Patrycja
dc.contributor.authorROJEK, KATARZYNA
dc.contributor.authorBernadzki, Krzysztof M.
dc.contributor.authorCicco, Teresa de
dc.contributor.authorPradhan, Bhola S.
dc.contributor.authorPrószyński, Tomasz
dc.contributor.authorNiewiadomski, Paweł
dc.contributor.authorPęziński, Marcin
dc.contributor.authorBijata, Monika
dc.contributor.authorBijata, Krystian
dc.contributor.authorWŁODARCZYK, JAKUB
dc.contributor.authorGawor, Marta
dc.date.accessioned2024-01-24T16:56:14Z
dc.date.available2024-01-24T16:56:14Z
dc.date.copyright2020-06-10
dc.date.issued2020
dc.description.accesstimeBEFORE_PUBLICATION
dc.description.financeŚrodki finansowe, o których mowa w art. 365 pkt. 2 ustawy
dc.description.versionOTHER
dc.description.volume13
dc.identifier.doi10.3389/FNMOL.2020.00104
dc.identifier.issn1662-5099
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/101130
dc.identifier.weblinkhttps://www.frontiersin.org/article/10.3389/fnmol.2020.00104/full
dc.languageeng
dc.pbn.affiliationbiological sciences
dc.relation.ispartofFrontiers in Molecular Neuroscience
dc.rightsCC-BY
dc.sciencecloudnosend
dc.titleArhgef5 Binds α-Dystrobrevin 1 and Regulates Neuromuscular Junction Integrity
dc.typeJournalArticle
dspace.entity.typePublication