Universität zu Köln

Rehorst, Wiebke A., Thelen, Maximilian P., Nolte, Hendrik, Tuerk, Clara, Cirak, Sebahattin, Peterson, Jonathan M., Wong, G. William, Wirth, Brunhilde ORCID: 0000-0003-4051-5191, Krueger, Marcus ORCID: 0000-0003-2008-4582, Winter, Dominic and Kye, Min Jeong ORCID: 0000-0002-1323-7256 (2019). Muscle regulates mTOR dependent axonal local translation in motor neurons via CTRP3 secretion: implications for a neuromuscular disorder, spinal muscular atrophy. Acta Neuropathol. Commun., 7 (1). LONDON: BMC. ISSN 2051-5960

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Abstract

Spinal muscular atrophy (SMA) is an inherited neuromuscular disorder, which causes dysfunction/loss of lower motor neurons and muscle weakness as well as atrophy. While SMA is primarily considered as a motor neuron disease, recent data suggests that survival motor neuron (SMN) deficiency in muscle causes intrinsic defects. We systematically profiled secreted proteins from control and SMN deficient muscle cells with two combined metabolic labeling methods and mass spectrometry. From the screening, we found lower levels of C1q/TNF-related protein 3 (CTRP3) in the SMA muscle secretome and confirmed that CTRP3 levels are indeed reduced in muscle tissues and serum of an SMA mouse model. We identified that CTRP3 regulates neuronal protein synthesis including SMN via mTOR pathway. Furthermore, CTRP3 enhances axonal outgrowth and protein synthesis rate, which are well-known impaired processes in SMA motor neurons. Our data revealed a new molecular mechanism by which muscles regulate the physiology of motor neurons via secreted molecules. Dysregulation of this mechanism contributes to the pathophysiology of SMA.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Rehorst, Wiebke A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Thelen, Maximilian P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nolte, Hendrik UNSPECIFIED UNSPECIFIED UNSPECIFIED Tuerk, Clara UNSPECIFIED UNSPECIFIED UNSPECIFIED Cirak, Sebahattin UNSPECIFIED UNSPECIFIED UNSPECIFIED Peterson, Jonathan M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wong, G. William UNSPECIFIED UNSPECIFIED UNSPECIFIED Wirth, Brunhilde UNSPECIFIED orcid.org/0000-0003-4051-5191 UNSPECIFIED Krueger, Marcus UNSPECIFIED orcid.org/0000-0003-2008-4582 UNSPECIFIED Winter, Dominic UNSPECIFIED UNSPECIFIED UNSPECIFIED Kye, Min Jeong UNSPECIFIED orcid.org/0000-0002-1323-7256 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-130874
DOI:	10.1186/s40478-019-0806-3
Journal or Publication Title:	Acta Neuropathol. Commun.
Volume:	7
Number:	1
Date:	2019
Publisher:	BMC
Place of Publication:	LONDON
ISSN:	2051-5960
Language:	English
Faculty:	Faculty of Mathematics and Natural Sciences
Divisions:	Faculty of Mathematics and Natural Sciences > Department of Biology > Institute for Genetics
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language MESSENGER-RNA; MOUSE MODELS; CELL-DEATH; SMN; EXPRESSION; SURVIVAL; PROTEINS; LOCALIZATION; DYSFUNCTION; ENDOCYTOSIS Multiple languages Neurosciences Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/13087