University of Oulu

Heikkinen, A., Härönen, H., Norman, O. and Pihlajaniemi, T. (2020), Collagen XIII and Other ECM Components in the Assembly and Disease of the Neuromuscular Junction. Anat Rec, 303: 1653-1663. doi:10.1002/ar.24092

Collagen XIII and other ECM components in the assembly and disease of the neuromuscular junction

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Author: Heikkinen, Anne1; Härönen, Heli1; Norman, Oula1;
Organizations: 1Oulu Center for Cell‐Matrix Research, Biocenter Oulu, Faculty of Biochemistry and Molecular Medicine, University of Oulu, Oulu, Finland
Format: article
Version: accepted version
Access: open
Online Access: PDF Full Text (PDF, 1.8 MB)
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Language: English
Published: John Wiley & Sons, 2019
Publish Date: 2020-02-15


Alongside playing structural roles, the extracellular matrix (ECM) acts as an interaction platform for cellular homeostasis, organ development, and maintenance. The necessity of the ECM is highlighted by the diverse, sometimes very serious diseases that stem from defects in its components. The neuromuscular junction (NMJ) is a large peripheral motor synapse differing from its central counterparts through the ECM included at the synaptic cleft. Such synaptic basal lamina (BL) is specialized to support NMJ establishment, differentiation, maturation, stabilization, and function and diverges in molecular composition from the extrasynaptic ECM. Mutations, toxins, and autoantibodies may compromise NMJ integrity and function, thereby leading to congenital myasthenic syndromes (CMSs), poisoning, and autoimmune diseases, respectively, and all these conditions may involve synaptic ECM molecules. With neurotransmission degraded or blocked, muscle function is impaired or even prevented. At worst, this can be fatal. The article reviews the synaptic BL composition required for assembly and function of the NMJ molecular machinery through the lens of studies primarily with mouse models but also with human patients. In‐depth focus is given to collagen XIII, a postsynaptic‐membrane‐spanning but also shed ECM protein that in recent years has been revealed to be a significant component for the NMJ. Its deficiency in humans causes CMS, and autoantibodies against it have been recognized in autoimmune myasthenia gravis. Mouse models have exposed numerous details that appear to recapitulate human NMJ phenotypes relatively faithfully and thereby can be readily used to generate information necessary for understanding and ultimately treating human diseases.

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Series: The anatomical record
ISSN: 1932-8486
ISSN-E: 1932-8494
ISSN-L: 1932-8486
Volume: 303
Issue: 6
Pages: 1653 - 1663
DOI: 10.1002/ar.24092
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3112 Neurosciences
Funding: Sigrid Jusélius Foundation; Academy of Finland, Grant number: 308867.
Academy of Finland Grant Number: 308867
Detailed Information: 308867 (Academy of Finland Funding decision)
Copyright information: © 2019 Wiley Periodicals, Inc. This is the peer reviewed version of the following article: Heikkinen, A. , Härönen, H. , Norman, O. and Pihlajaniemi, T. (2019), Collagen XIII and Other ECM Components in the Assembly and Disease of the Neuromuscular Junction. Anat Rec. doi:10.1002/ar.24092, which has been published in final form at This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.