Please use this identifier to cite or link to this item: https://hdl.handle.net/10356/159382
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-. https://dx.doi.org/10.7554/eLife.66596
Project: 2015-T1-001-035 
MOE2016-T3-1-005 
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.
URI: https://hdl.handle.net/10356/159382
ISSN: 2050-084X
DOI: 10.7554/eLife.66596
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

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