Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling

Abstract Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusiv...

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Autores principales:	Ahmad Abdullah, Carl Herdenberg, Håkan Hedman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/28591f96dd0a4e8aaa555ae108212a98
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spelling	oai:doaj.org-article:28591f96dd0a4e8aaa555ae108212a982021-12-02T13:39:34ZNetrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling10.1038/s41598-021-87949-72045-2322https://doaj.org/article/28591f96dd0a4e8aaa555ae108212a982021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87949-7https://doaj.org/toc/2045-2322Abstract Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.Ahmad AbdullahCarl HerdenbergHåkan HedmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ahmad Abdullah Carl Herdenberg Håkan Hedman Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
description	Abstract Netrin-1 is a secreted protein that is well known for its involvement in axonal guidance during embryonic development and as an enhancer of cancer cell metastasis. Despite extensive efforts, the molecular mechanisms behind many of the physiological functions of netrin-1 have remained elusive. Here, we show that netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling in various cellular systems, including a mutually inhibitory interaction with the BMP-promoting function of leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins. The BMP inhibitory function of netrin-1 in mouse embryonic fibroblasts was dependent on the netrin receptor neogenin, with the expression level regulated by both netrin-1 and LRIG proteins. Our results reveal a previously unrecognized function of netrin-1 that may help to explain several of the developmental, physiological, and cancer-promoting functions of netrins at the signal transduction level.
format	article
author	Ahmad Abdullah Carl Herdenberg Håkan Hedman
author_facet	Ahmad Abdullah Carl Herdenberg Håkan Hedman
author_sort	Ahmad Abdullah
title	Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
title_short	Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
title_full	Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
title_fullStr	Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
title_full_unstemmed	Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling
title_sort	netrin-1 functions as a suppressor of bone morphogenetic protein (bmp) signaling
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/28591f96dd0a4e8aaa555ae108212a98
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Netrin-1 functions as a suppressor of bone morphogenetic protein (BMP) signaling

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