The role of drebrin in the neuromuscular junction

• Autorzy: Alvarez-Suarez P. , Gawor M. , Proszynski T.J.
• Języki publikacji: EN

Abstrakty

EN

INTRODUCTION: Drebrin is an actin-binding protein that regulates cytoskeleton dynamics in different cell types. It plays an important role in shaping dendritic spines and facilitating the stabilization of neurotransmitter receptors at the postsynaptic membrane in the CNS. Its role at the neuromuscular junction (NMJ) in the PNS has not been investigated. AIM(S): In the present study we aimed to explore the role of Drebrin in this special type of synapse and to study its mechanism of action. METHOD(S): We used an in vitro model of C2C12‑derived myotubes in which Drebrin1 expression is silenced with siRNA or its actin-binding function is blocked by a BTP2 inhibitor. To address the role of Drebrin at the postsynaptic machinery, we used both biochemical and immunohistochemical approaches. RESULTS: We found that Drebrin colocalizes with acetylcholine receptors (AChR) at the surface of myofibers in vivo and in vitro, and its depletion causes impairments in receptor aggregation and clusters complexity, suggesting a crucial role in the regulation of these processes. We assessed whether drebrin inhibition affects the expression levels and cell surface delivery of AChRs or the microtubule organization underneath AChRs. Our experiments revealed that drebrin depletion in cultured myotubes affects the organization of cortical microtubules, which has been previously shown to be indispensable for incorporation of newly synthesized AChR into the postsynaptic specialization. CONCLUSIONS: We found that Drebrin is a component of the muscle postsynaptic machinery and it plays an important role in their organization. The mechanism through which Drebrin regulates AChR clustering appears to occur through its interaction with EB3, that leads to the recruitment of microtubules and allows the stabilization of AChRs. FINANCIAL SUPPORT: This research was supported by the National Science Centre grants: UMO‑2018/29/B/ NZ3/02675, UMO‑2016/21/D/NZ4/03069, and UMO- ‑2018/29/N/NZ3/02682.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2019
• Tom: 79
• Numer: Suppl.1
• Opis fizyczny: p.XLVIII

Twórcy

autor

Alvarez-Suarez P.

• Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Gawor M.

• Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland

autor

Proszynski T.J.

• Laboratory of Synaptogenesis, Nencki Institute of Experimental Biology, Polish Academy of Sciences, Warsaw, Poland