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Open AccessArticle

Intracellular Localization in Zebrafish Muscle and Conserved Sequence Features Suggest Roles for Gelatinase A Moonlighting in Sarcomere Maintenance

1
Department of Biology, University of New Brunswick, Fredericton, NB E3B 5A3, Canada
2
Department of Physiology & Pharmacology, University of Calgary, Calgary, AB T2N 4N1, Canada
3
Department of Oral Biological and Medical Sciences and Centre for Blood Research, University of British Columbia, Vancouver, BC V6T 1Z4, Canada
*
Author to whom correspondence should be addressed.
Biomedicines 2019, 7(4), 93; https://doi.org/10.3390/biomedicines7040093
Received: 7 November 2019 / Revised: 19 November 2019 / Accepted: 25 November 2019 / Published: 29 November 2019
(This article belongs to the Special Issue Zebrafish Models for Development and Disease 2.0)
Gelatinase A (Mmp2 in zebrafish) is a well-characterized effector of extracellular matrix remodeling, extracellular signaling, and along with other matrix metalloproteinases (MMPs) and extracellular proteases, it plays important roles in the establishment and maintenance of tissue architecture. Gelatinase A is also found moonlighting inside mammalian striated muscle cells, where it has been implicated in the pathology of ischemia-reperfusion injury. Gelatinase A has no known physiological function in muscle cells, and its localization within mammalian cells appears to be due to inefficient recognition of its N-terminal secretory signal. Here we show that Mmp2 is abundant within the skeletal muscle cells of zebrafish, where it localizes to the M-line of sarcomeres and degrades muscle myosin. The N-terminal secretory signal of zebrafish Mmp2 is also challenging to identify, and this is a conserved characteristic of gelatinase A orthologues, suggesting a selective pressure acting to prevent the efficient secretion of this protease. Furthermore, there are several strongly conserved phosphorylation sites within the catalytic domain of gelatinase A orthologues, some of which are phosphorylated in vivo, and which are known to regulate the activity of this protease. We conclude that gelatinase A likely participates in uncharacterized physiological functions within the striated muscle, possibly in the maintenance of sarcomere proteostasis, that are likely regulated by kinases and phosphatases present in the sarcomere. View Full-Text
Keywords: Gelatinase A; Mmp2; zebrafish; sarcomere; myosin; proteostasis; phosphorylation; TAILS; secretion Gelatinase A; Mmp2; zebrafish; sarcomere; myosin; proteostasis; phosphorylation; TAILS; secretion
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Fallata, A.M.; Wyatt, R.A.; Levesque, J.M.; Dufour, A.; Overall, C.M.; Crawford, B.D. Intracellular Localization in Zebrafish Muscle and Conserved Sequence Features Suggest Roles for Gelatinase A Moonlighting in Sarcomere Maintenance. Biomedicines 2019, 7, 93.

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