Dublin Core
Title
Zebrafish Models for Development and Disease 2.0
Subject
Gelatinase A; Mmp2; zebrafish; sarcomere; myosin; proteostasis; phosphorylation; TAILS;
secretion, Fish, Fisheris
secretion, Fish, Fisheris
Description
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.
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.
Creator
Editors
James A. Marrs
Swapnalee Sarmah
James A. Marrs
Swapnalee Sarmah
Source
https://www.mdpi.com/books/book/6196-zebrafish-models-for-development-and-disease-2-0
Publisher
MDPI
Date
2022
Contributor
Jadik Wijayanto
Rights
The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons
license CC BY-NC-ND.
license CC BY-NC-ND.
Relation
https://www.mdpi.com
Format
PDF
Language
English
Type
Textbook
Identifier
ISBN 978-3-0365-5459-4 (Hbk)
ISBN 978-3-0365-5460-0 (PDF)
ISBN 978-3-0365-5460-0 (PDF)
Coverage
St. Alban-Anlage 66
4052 Basel, Switzerland
4052 Basel, Switzerland