Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts

Abstract The (pro)renin receptor (PRR) is a multifunctional integral membrane protein that serves as a component of the vacuolar H+-ATPase (V-ATPase) and also activates (pro)renin. We recently showed that full-length PRR, found as part of a V-ATPase sub-complex, is abundant in extracellular vesicles...

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Autores principales:	Jonathan B. Murray, Christy Mikhael, Guanghong Han, Lorraine Perciliano de Faria, Wellington J. Rody, L. Shannon Holliday
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/726b5d06cd4c4dac8379069a60fd4cb3
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spelling	oai:doaj.org-article:726b5d06cd4c4dac8379069a60fd4cb32021-12-02T17:39:19ZActivation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts10.1038/s41598-021-88665-y2045-2322https://doaj.org/article/726b5d06cd4c4dac8379069a60fd4cb32021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88665-yhttps://doaj.org/toc/2045-2322Abstract The (pro)renin receptor (PRR) is a multifunctional integral membrane protein that serves as a component of the vacuolar H+-ATPase (V-ATPase) and also activates (pro)renin. We recently showed that full-length PRR, found as part of a V-ATPase sub-complex, is abundant in extracellular vesicles shed by osteoclasts. Here, we tested whether these extracellular vesicles stimulate (pro)renin. Extracellular vesicles isolated from the conditioned media of RAW 264.7 osteoclast-like cells or primary osteoclasts were characterized and counted by nanoparticle tracking. Immunoblotting confirmed that full-length PRR was present. Extracellular vesicles from osteoclasts dose-dependently stimulated (pro)renin activity, while extracellular vesicles from 4T1 cancer cells, in which we did not detect PRR, did not activate (pro)renin. To confirm that the ability of extracellular vesicles from osteoclasts to stimulate (pro)renin activity was due to the PRR, the “handle region peptide” from the PRR, a competitive inhibitor of PRR activity, was tested. It dose-dependently blocked the ability of extracellular vesicles to stimulate the enzymatic activity of (pro)renin. In summary, the PRR, an abundant component of extracellular vesicles shed by osteoclasts, stimulates (pro)renin activity. This represents a novel mechanism by which extracellular vesicles can function in intercellular regulation, with direct implications for bone biology.Jonathan B. MurrayChristy MikhaelGuanghong HanLorraine Perciliano de FariaWellington J. RodyL. Shannon HollidayNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-8 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jonathan B. Murray Christy Mikhael Guanghong Han Lorraine Perciliano de Faria Wellington J. Rody L. Shannon Holliday Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts
description	Abstract The (pro)renin receptor (PRR) is a multifunctional integral membrane protein that serves as a component of the vacuolar H+-ATPase (V-ATPase) and also activates (pro)renin. We recently showed that full-length PRR, found as part of a V-ATPase sub-complex, is abundant in extracellular vesicles shed by osteoclasts. Here, we tested whether these extracellular vesicles stimulate (pro)renin. Extracellular vesicles isolated from the conditioned media of RAW 264.7 osteoclast-like cells or primary osteoclasts were characterized and counted by nanoparticle tracking. Immunoblotting confirmed that full-length PRR was present. Extracellular vesicles from osteoclasts dose-dependently stimulated (pro)renin activity, while extracellular vesicles from 4T1 cancer cells, in which we did not detect PRR, did not activate (pro)renin. To confirm that the ability of extracellular vesicles from osteoclasts to stimulate (pro)renin activity was due to the PRR, the “handle region peptide” from the PRR, a competitive inhibitor of PRR activity, was tested. It dose-dependently blocked the ability of extracellular vesicles to stimulate the enzymatic activity of (pro)renin. In summary, the PRR, an abundant component of extracellular vesicles shed by osteoclasts, stimulates (pro)renin activity. This represents a novel mechanism by which extracellular vesicles can function in intercellular regulation, with direct implications for bone biology.
format	article
author	Jonathan B. Murray Christy Mikhael Guanghong Han Lorraine Perciliano de Faria Wellington J. Rody L. Shannon Holliday
author_facet	Jonathan B. Murray Christy Mikhael Guanghong Han Lorraine Perciliano de Faria Wellington J. Rody L. Shannon Holliday
author_sort	Jonathan B. Murray
title	Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts
title_short	Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts
title_full	Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts
title_fullStr	Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts
title_full_unstemmed	Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts
title_sort	activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/726b5d06cd4c4dac8379069a60fd4cb3
work_keys_str_mv	AT jonathanbmurray activationofproreninbyproreninreceptorinextracellularvesiclesfromosteoclasts AT christymikhael activationofproreninbyproreninreceptorinextracellularvesiclesfromosteoclasts AT guanghonghan activationofproreninbyproreninreceptorinextracellularvesiclesfromosteoclasts AT lorrainepercilianodefaria activationofproreninbyproreninreceptorinextracellularvesiclesfromosteoclasts AT wellingtonjrody activationofproreninbyproreninreceptorinextracellularvesiclesfromosteoclasts AT lshannonholliday activationofproreninbyproreninreceptorinextracellularvesiclesfromosteoclasts
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Activation of (pro)renin by (pro)renin receptor in extracellular vesicles from osteoclasts

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