PUBLICATION
Intracellular Localization in Zebrafish Muscle and Conserved Sequence Features Suggest Roles for Gelatinase A Moonlighting in Sarcomere Maintenance
- Authors
- Fallata, A.M., Wyatt, R.A., Levesque, J.M., Dufour, A., Overall, C.M., Crawford, B.D.
- ID
- ZDB-PUB-191206-2
- Date
- 2019
- Source
- Biomedicines 7(4): (Journal)
- Registered Authors
- Crawford, Bryan D., Wyatt, Rachael
- Keywords
- Gelatinase A, Mmp2, TAILS, myosin, phosphorylation, proteostasis, sarcomere, secretion, zebrafish
- MeSH Terms
- none
- PubMed
- 31795436 Full text @ Biomedicines
Citation
Fallata, A.M., Wyatt, R.A., Levesque, J.M., Dufour, A., Overall, C.M., Crawford, B.D. (2019) Intracellular Localization in Zebrafish Muscle and Conserved Sequence Features Suggest Roles for Gelatinase A Moonlighting in Sarcomere Maintenance. Biomedicines. 7(4):.
Abstract
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping