Please use this identifier to cite or link to this item:
Title: Matriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX
Authors: Ma, Jiajia
Scott, Claire A.
Ho, Ying Na
Mahabaleshwar, Harsha
Marsay, Katherine S.
Zhang, Changqing
Teow, Christopher K. J.
Ng, Ser Sue
Zhang, Weibin
Tergaonkar, Vinay
Partridge, Lynda J.
Roy, Sudipto
Amaya, Enrique
Carney, Tom J.
Keywords: Science::Medicine
Issue Date: 2021
Source: Ma, J., Scott, C. A., Ho, Y. N., Mahabaleshwar, H., Marsay, K. S., Zhang, C., Teow, C. K. J., Ng, S. S., Zhang, W., Tergaonkar, V., Partridge, L. J., Roy, S., Amaya, E. & Carney, T. J. (2021). Matriptase activation of Gq drives epithelial disruption and inflammation via RSK and DUOX. ELife, 10, e66596-.
Project: 2015-T1-001-035 
Journal: eLife 
Abstract: Epithelial tissues are primed to respond to insults by activating epithelial cell motility and rapid inflammation. Such responses are also elicited upon overexpression of the membrane-bound protease, Matriptase, or mutation of its inhibitor, Hai1. Unrestricted Matriptase activity also predisposes to carcinoma. How Matriptase leads to these cellular outcomes is unknown. We demonstrate that zebrafish hai1a mutants show increased H2O2, NfκB signalling, and IP3R -mediated calcium flashes, and that these promote inflammation, but do not generate epithelial cell motility. In contrast, inhibition of the Gq subunit in hai1a mutants rescues both the inflammation and epithelial phenotypes, with the latter recapitulated by the DAG analogue, PMA. We demonstrate that hai1a has elevated MAPK pathway activity, inhibition of which rescues the epidermal defects. Finally, we identify RSK kinases as MAPK targets disrupting adherens junctions in hai1a mutants. Our work maps novel signalling cascades mediating the potent effects of Matriptase on epithelia, with implications for tissue damage response and carcinoma progression.
ISSN: 2050-084X
DOI: 10.7554/eLife.66596
Schools: Lee Kong Chian School of Medicine (LKCMedicine) 
Organisations: Institute of Molecular and Cell Biology, A*STAR
Rights: © 2021 Ma et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:LKCMedicine Journal Articles

Files in This Item:
File Description SizeFormat 
elife-66596-v2.pdf12.27 MBAdobe PDFThumbnail

Citations 50

Updated on Feb 18, 2024

Web of ScienceTM
Citations 50

Updated on Oct 28, 2023

Page view(s)

Updated on Feb 27, 2024

Download(s) 50

Updated on Feb 27, 2024

Google ScholarTM




Items in DR-NTU are protected by copyright, with all rights reserved, unless otherwise indicated.