RT Journal Article
SR Electronic
T1 SH3BP2 regulates the organization of the neuromuscular synapses through protein-driven phase separation
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2024.05.23.595491
DO 10.1101/2024.05.23.595491
A1 Pradhan, Bhola Shankar
A1 Bernadzki, Krzysztof
A1 Bandaruk, Yauhen
A1 Siudzińska, Anna
A1 De Cicco, Teresa
A1 Gawor, Marta
A1 Krzemień, Joanna
A1 Chodaczek, Grzegorz
A1 Hashemolhosseini, Said
A1 Prószyński, Tomasz J.
YR 2024
UL http://biorxiv.org/content/early/2024/05/23/2024.05.23.595491.abstract
AB The molecular mechanisms underlying the development and maintenance of the neuromuscular junction are poorly understood, even though the malfunction of these specialized synapses is associated with severe genetic and autoimmune disorders. The identity of factors controlling the maintenance mechanisms of postsynaptic acetylcholine receptors (AChR) in high-density has been elusive and is of great interest to the pharma industry, searching for possible new targets for disease interventions. Here, we report the identification of a scaffold protein SH3BP2, which exhibits polyvalent interaction with the dystrophin-glycoprotein complex (DGC) and AChR pentamers, promoting AChR clustering through phase separation. Muscle-specific SH3BP2 deletion in mice leads to impaired organization of the neuromuscular synapses, defects in synaptic transmission, and reduced muscle strength. Our studies identified a novel regulator of the postsynaptic machinery involved in clustering AChR and linking it to the DGC.Competing Interest StatementThe authors have declared no competing interest.