Universität zu Köln

Kaplan, Mehmet Mahsum ORCID: 0000-0002-3013-0848, Sultana, Nasreen, Benedetti, Ariane, Obermair, Gerald J., Linde, Nina F., Papadopoulos, Symeon, Dayal, Anamika ORCID: 0000-0001-8075-8812, Grabner, Manfred and Flucher, Bernhard E. (2018). Calcium Influx and Release Cooperatively Regulate AChR Patterning and Motor Axon Outgrowth during Neuromuscular Junction Formation. Cell Reports, 23 (13). S. 3891 - 3905. CAMBRIDGE: CELL PRESS. ISSN 2211-1247

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Abstract

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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kaplan, Mehmet Mahsum UNSPECIFIED orcid.org/0000-0002-3013-0848 UNSPECIFIED Sultana, Nasreen UNSPECIFIED UNSPECIFIED UNSPECIFIED Benedetti, Ariane UNSPECIFIED UNSPECIFIED UNSPECIFIED Obermair, Gerald J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Linde, Nina F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Papadopoulos, Symeon UNSPECIFIED UNSPECIFIED UNSPECIFIED Dayal, Anamika UNSPECIFIED orcid.org/0000-0001-8075-8812 UNSPECIFIED Grabner, Manfred UNSPECIFIED UNSPECIFIED UNSPECIFIED Flucher, Bernhard E. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-182567
DOI:	10.1016/j.celrep.2018.05.085
Journal or Publication Title:	Cell Reports
Volume:	23
Number:	13
Page Range:	S. 3891 - 3905
Date:	2018
Publisher:	CELL PRESS
Place of Publication:	CAMBRIDGE
ISSN:	2211-1247
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language RECEPTOR GENE-EXPRESSION; CHANNEL SPLICE VARIANT; PROTEIN-KINASE-C; DIHYDROPYRIDINE RECEPTOR; SYNAPSE FORMATION; MUSCLE-ACTIVITY; SARCOPLASMIC-RETICULUM; IN-VIVO; SKELETAL; NERVE Multiple languages Cell Biology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/18256