INTRODUCTION: Neuromuscular junctions (NMJs) are specialized synapses formed between the motor neurons and skeletal muscles. The proper functioning of the NMJ is important for activities involving muscle contraction including breathing. Liprin‑α‑1 was previously identified in a biochemical screen as an interactor of α‑dystrobrevin‑1, a component of dystrophin-associated glycoprotein complex (DGC) responsible for the attachment of the postsynaptic machinery to the extracellular matrix. Liprin‑α‑1 has been shown to be an organizer of synapses in the central nervous system and our study presents an insight into the localization and function of this protein at the vertebrate NMJ. AIM(S): To unravel the localization and function of liprin‑α‑1 at the vertebrate NMJ. METHOD(S): We employed immunohistochemical, siRNA-mediated RNAi techniques and confocal microscopy techniques. RESULTS: We show that liprin‑α‑1 localizes to the postsynaptic site of NMJ in a nerve-dependent manner, and its localization is maintained throughout postnatal development. Liprin‑α‑1 plays a crucial role in the formation of the postsynaptic machinery since liprin‑α‑1 depleted myotubes failed to cluster postsynaptic acetylcholine receptors (AChRs). We provide evidence that liprin‑α‑1 plays a role in the attachment of microtubule ends to the cell cortex, where they stabilize the postsynaptic machinery and promote clustering of AChRs. Consistently with this observation abrupt disruption of microtubules with in cultured myotubes did not affected preexisting AChR clusters, but abolished formation of the new assemblies. CONCLUSIONS: Our results show that Liprin‑α‑1 is important component of the postsynaptic machinery involved in AChR clustering. FINANCIAL SUPPORT: This research was supported by the NCN grants 2012/05/E/NZ3/00487, 2015/19/N/ NZ5/02268, 2014/13/B/NZ3/00909, and 2013/09/B/ NZ3/03524.
JavaScript jest wyłączony w Twojej przeglądarce internetowej. Włącz go, a następnie odśwież stronę, aby móc w pełni z niej korzystać.