University of Oulu

Härönen, H, Zainul, Z, Naumenko, N, et al. Correct expression and localization of collagen XIII are crucial for the normal formation and function of the neuromuscular system. Eur J Neurosci. 2019; 49: 1491– 1511. https://doi.org/10.1111/ejn.14346

Correct expression and localization of collagen XIII are crucial for the normal formation and function of the neuromuscular system

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Author: Härönen, Heli1; Zainul, Zarin2; Naumenko, Nikolay3;
Organizations: 1Faculty of Biochemistry and Molecular Medicine, Center for Cell‐Matrix Research, Biocenter Oulu, University of Oulu, Oulu, Finland
2Department of Pediatrics, College of Medicine, University of Florida, Gainesville, Florida
3Department of Biotechnology and Molecular Medicine, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
4Biocenter Oulu Electron Microscopy Core Facility, University of Oulu, Oulu, Finland
5Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, University of Eastern Finland, Kuopio, Finland
6Laboratory of Neurobiology, Department of Physiology, Kazan Federal University, Kazan, Russia
7Faculty of Biology, Medicine and Health, Division of Cell Matrix Biology and Regenerative Medicine, University of Manchester, Manchester, UK
Format: article
Version: accepted version
Access: embargoed
Persistent link: http://urn.fi/urn:nbn:fi-fe201902205808
Language: English
Published: John Wiley & Sons, 2019
Publish Date: 2020-01-22
Description:

Abstract

Transmembrane collagen XIII has been linked to maturation of the musculoskeletal system. Its absence in mice (Col13a1−/−) results in impaired neuromuscular junction (NMJ) differentiation and function, while transgenic overexpression (Col13a1oe) leads to abnormally high bone mass. Similarly, loss‐of‐function mutations in COL13A1 in humans produce muscle weakness, decreased motor synapse function and mild dysmorphic skeletal features. Here, analysis of the exogenous overexpression of collagen XIII in various muscles revealed highly increased transcript and protein levels, especially in the diaphragm. Unexpectedly, the main location of exogenous collagen XIII in the muscle was extrasynaptic, in fibroblast‐like cells, while some motor synapses were devoid of collagen XIII, possibly due to a dominant negative effect. Concomitantly, phenotypical changes in the NMJs of the Col13a1oe mice partly resembled those previously observed in Col13a1−/− mice. Namely, the overall increase in collagen XIII expression in the muscle produced both pre‐ and postsynaptic abnormalities at the NMJ, especially in the diaphragm. We discovered delayed and compromised acetylcholine receptor (AChR) clustering, axonal neurofilament aggregation, patchy acetylcholine vesicle (AChV) accumulation, disrupted adhesion of the nerve and muscle, Schwann cell invagination and altered evoked synaptic function. Furthermore, the patterns of the nerve trunks and AChR clusters in the diaphragm were broader in the adult muscles, and already prenatally in the Col13a1−/− mice, suggesting collagen XIII involvement in the development of the neuromuscular system. Overall, these results confirm the role of collagen XIII at the neuromuscular synapses and highlight the importance of its correct expression and localization for motor synapse formation and function.

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Series: European journal of neuroscience
ISSN: 0953-816X
ISSN-E: 1460-9568
ISSN-L: 0953-816X
Volume: 49
Issue: 11
Pages: 1491 - 1511
DOI: 10.1111/ejn.14346
OADOI: https://oadoi.org/10.1111/ejn.14346
Type of Publication: A1 Journal article – refereed
Field of Science: 3111 Biomedicine
Subjects:
Funding: This work was supported by the Sigrid Jusélius Foundation and the University of Oulu Graduate School through the Biocenter Oulu doctoral program.
Copyright information: © 2019 Federation of European Neuroscience Societies and John Wiley & Sons Ltd. This is the peer reviewed version of the following article:Härönen H, Zainul Z, Naumenko N, et al. Correct expression and localization of collagen XIII are crucial for the normal formation and function of the neuromuscular system. Eur J Neurosci. 2019; 49: 1491– 1511, which has been published in final form at https://doi.org/10.1111/ejn.14346. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.