Molecular control of neuromuscular junction development

Journal of Cachexia, Sarcopenia and Muscle

Ferraro Elisabetta¹  Molinari Francesca¹ 

[1] Pathophysiology and Treatment of Cachexia Unit, IRCCS San Raffaele Pisana Institute, Rome

关键词: Neuromuscular junction;    Postsynaptical differentiation;    AChR transcription;    Sarcopenia;    Congenital myastenic syndromes;    Agrin–MuSK pathway;   

DOI  :  10.1007/s13539-011-0041-7

来源: Wiley

【 摘 要 】

Abstract

Skeletal muscle innervation is a multi-step process leading to the neuromuscular junction (NMJ) apparatus formation. The transmission of the signal from nerve to muscle occurs at the NMJ level. The molecular mechanism that orchestrates the organization and functioning of synapses is highly complex, and it has not been completely elucidated so far. Neuromuscular junctions are assembled on the muscle fibers at very precise locations called end plates (EP). Acetylcholine receptor (AChR) clusterization at the end plates is required for an accurate synaptic transmission. This review will focus on some mechanisms responsible for accomplishing the correct distribution of AChRs at the synapses. Recent evidences support the concept that a dual transcriptional control of AChR genes in subsynaptic and extrasynaptic nuclei is crucial for AChR clusterization. Moreover, new players have been discovered in the agrin–MuSK pathway, the master organizer of postsynaptical differentiation. Mutations in this pathway cause neuromuscular congenital disorders. Alterations of the postynaptic apparatus are also present in physiological conditions characterized by skeletal muscle wasting. Indeed, recent evidences demonstrate how NMJ misfunctioning has a crucial role at the onset of age-associated sarcopenia.

【 授权许可】

CC BY-NC   
© 2012 The Authors. Published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.