University of Oulu

Zarin Zainul, Anne Heikkinen, Hennariikka Koivisto, Iina Rautalahti, Mika Kallio, Shuo Lin, Heli Härönen, Oula Norman, Markus A. Rüegg, Heikki Tanila, Taina Pihlajaniemi. Collagen XIII Is Required for Neuromuscular Synapse Regeneration and Functional Recovery after Peripheral Nerve Injury. Journal of Neuroscience 25 April 2018, 38 (17) 4243-4258; DOI: 10.1523/JNEUROSCI.3119-17.2018

Collagen XIII is required for neuromuscular synapse regeneration and functional recovery after peripheral nerve injury

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Author: Zainul, Zarin1; Heikkinen, Anne1; Koivisto, Hennariikka2;
Organizations: 1Center for Cell-Matrix Research, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, 90014 Oulu, Finland
2A.I. Virtanen Institute, University of Eastern Finland, 70211 Kuopio, Finland
3Department of Clinical Neurophysiology, Oulu University Hospital, 90220 Oulu, Finland
4Medical Imaging Physics and Technology-Research Group, University of Oulu, 90220 Oulu, Finland
5Biozentrum, University of Basel, CH-4056 Basel, Switzerland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 5.6 MB)
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Language: English
Published: Society for Neuroscience, 2018
Publish Date: 2018-10-25


Collagen XIII occurs as both a transmembrane-bound and a shed extracellular protein and is able to regulate the formation and function of neuromuscular synapses. Its absence results in myasthenia: presynaptic and postsynaptic defects at the neuromuscular junction (NMJ), leading to destabilization of the motor nerves, muscle regeneration and atrophy. Mutations in COL13A1 have recently been found to cause congenital myasthenic syndrome, characterized by fatigue and chronic muscle weakness, which may be lethal. We show here that muscle defects in collagen XIII-deficient mice stabilize in adulthood, so that the disease is not progressive until very late. Sciatic nerve crush was performed to examine how the lack of collagen XIII or forced expression of its transmembrane form affects the neuromuscular synapse regeneration and functional recovery following injury. We show that collagen XIII-deficient male mice are unable to achieve complete NMJ regeneration and functional recovery. This is mainly attributable to presynaptic defects that already existed in the absence of collagen XIII before injury. Shedding of the ectodomain is not required, as the transmembrane form of collagen XIII alone fully rescues the phenotype. Thus, collagen XIII could serve as a therapeutic agent in cases of injury-induced PNS regeneration and functional recovery. We conclude that intrinsic alterations at the NMJ in Col13a1−/− mice contribute to impaired and incomplete NMJ regeneration and functional recovery after peripheral nerve injury. However, such alterations do not progress once they have stabilized in early adulthood, emphasizing the role of collagen XIII in NMJ maturation.

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Series: The Journal of neuroscience
ISSN: 0270-6474
ISSN-E: 1529-2401
ISSN-L: 0270-6474
Volume: 38
Issue: 17
Pages: 4243 - 4258
DOI: 10.1523/JNEUROSCI.3119-17.2018
Type of Publication: A1 Journal article – refereed
Field of Science: 1182 Biochemistry, cell and molecular biology
Funding: This work was supported by the University of Oulu Graduate School, Biocenter Oulu Doctoral Program, Center of Excellence Program 2012–2017 of the Academy of Finland Grant 284605 to T.P., and the Sigrid Jusélius Foundation.
Academy of Finland Grant Number: 284605
Detailed Information: 284605 (Academy of Finland Funding decision)
Copyright information: Copyright © 2018 the authors.