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Collagen XIII Is Required for Neuromuscular Synapse Regeneration and Functional Recovery after Peripheral Nerve Injury

Zainul, Zarin and Heikkinen, Anne and Koivisto, Hennariikka and Rautalahti, Iina and Kallio, Mika and Lin, Shuo and Härönen, Heli and Norman, Oula and Rüegg, Markus A. and Tanila, Heikki and Pihlajaniemi, Taina. (2018) Collagen XIII Is Required for Neuromuscular Synapse Regeneration and Functional Recovery after Peripheral Nerve Injury. The Journal of neuroscience, 38 (17). pp. 4243-4258.

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Abstract

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.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Computational & Systems Biology > Bioinformatics (Schwede)
05 Faculty of Science > Departement Biozentrum > Neurobiology > Pharmacology/Neurobiology (Rüegg)
UniBasel Contributors:Rüegg, Markus A.
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Society for Neuroscience
e-ISSN:1529-2401
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:12 Apr 2019 12:39
Deposited On:18 Mar 2019 15:44

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