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, 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

Full text not available from this repository.

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:
CreatorsEmailORCIDORCID Put Code
Rehorst, Wiebke A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thelen, Maximilian P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nolte, HendrikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tuerk, ClaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cirak, SebahattinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peterson, Jonathan M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wong, G. WilliamUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wirth, BrunhildeUNSPECIFIEDorcid.org/0000-0003-4051-5191UNSPECIFIED
Krueger, MarcusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Winter, DominicUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kye, Min JeongUNSPECIFIEDorcid.org/0000-0002-1323-7256UNSPECIFIED
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: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
MESSENGER-RNA; MOUSE MODELS; CELL-DEATH; SMN; EXPRESSION; SURVIVAL; PROTEINS; LOCALIZATION; DYSFUNCTION; ENDOCYTOSISMultiple languages
NeurosciencesMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/13087

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item