Arhgef5 Binds α-Dystrobrevin 1 and Regulates Neuromuscular Junction Integrity.

Autor:	Bernadzki KM; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland., Daszczuk P; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland., Rojek KO; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland.; Institute of Physical Chemistry, Polish Academy of Sciences, Warsaw, Poland., Pęziński M; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland., Gawor M; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland., Pradhan BS; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland., de Cicco T; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland., Bijata M; Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Warsaw, Poland., Bijata K; Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Warsaw, Poland., Włodarczyk J; Laboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Warsaw, Poland., Prószyński TJ; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland.; Łukasiewicz Research Network - PORT Polish Center for Technology Development, Wrocław, Poland., Niewiadomski P; Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Warsaw, Poland.; Laboratory of Molecular and Cellular Signaling, Centre of New Technologies, University of Warsaw, Warsaw, Poland.
Jazyk:	angličtina
Zdroj:	Frontiers in molecular neuroscience [Front Mol Neurosci] 2020 Jun 10; Vol. 13, pp. 104. Date of Electronic Publication: 2020 Jun 10 (Print Publication: 2020).
DOI:	10.3389/fnmol.2020.00104
Abstrakt:	The 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 α-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 loss in vivo is 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. (Copyright © 2020 Bernadzki, Daszczuk, Rojek, Pęziński, Gawor, Pradhan, de Cicco, Bijata, Bijata, Włodarczyk, Prószyński and Niewiadomski.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu