Calcium Influx and Release Cooperatively Regulate AChR Patterning and Motor Axon Outgrowth during Neuromuscular Junction Formation

被引:21
作者
Kaplan, Mehmet Mahsum [1 ]
Sultana, Nasreen [1 ]
Benedetti, Ariane [1 ]
Obermair, Gerald J. [1 ]
Linde, Nina F. [2 ]
Papadopoulos, Symeon [2 ]
Dayal, Anamika [3 ]
Grabner, Manfred [3 ]
Flucher, Bernhard E. [1 ]
机构
[1] Med Univ Innsbruck, Dept Physiol & Med Phys, A-6020 Innsbruck, Austria
[2] Univ Cologne, Inst Vegetat Physiol, Ctr Physiol & Pathophysiol, D-50931 Cologne, Germany
[3] Med Univ Innsbruck, Dept Med Genet Mol & Clin Pharmacol, A-6020 Innsbruck, Austria
来源
CELL REPORTS | 2018年 / 23卷 / 13期
基金
奥地利科学基金会;
关键词
RECEPTOR GENE-EXPRESSION; CHANNEL SPLICE VARIANT; PROTEIN-KINASE-C; DIHYDROPYRIDINE RECEPTOR; SYNAPSE FORMATION; MUSCLE-ACTIVITY; SARCOPLASMIC-RETICULUM; IN-VIVO; SKELETAL; NERVE;
D O I
10.1016/j.celrep.2018.05.085
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Formation of synapses between motor neurons and muscles is initiated by clustering of acetylcholine receptors (AChRs) in the center of muscle fibers prior to nerve arrival. This AChR patterning is considered to be critically dependent on calcium influx through L-type channels (Ca v 1.1). Using a genetic approach in mice, we demonstrate here that either the L-type calcium currents (LTCCs) or sarcoplasmic reticulum (SR) calcium release is necessary and sufficient to regulate AChR clustering at the onset of neuromuscular junction (NMJ) development. The combined lack of both calcium signals results in loss of AChR patterning and excessive nerve branching. In the absence of SR calcium release, the severity of synapse formation defects inversely correlates with the magnitude of LTCCs. These findings highlight the importance of activity-dependent calcium signaling in early neuromuscular junction formation and indicate that both LTCC and SR calcium release individually support proper innervation of muscle by regulating AChR patterning and motor axon outgrowth.
引用
收藏
页码:3891 / 3904
页数:14
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