Cargando…

Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme

Hectd1 mutant mouse embryos exhibit the neural tube defect exencephaly associated with abnormal cranial mesenchyme. Cellular rearrangements in cranial mesenchyme are essential during neurulation for elevation of the neural folds. Here we investigate the molecular basis of the abnormal behavior of He...

Descripción completa

Detalles Bibliográficos
Autores principales: Sarkar, Anjali A., Zohn, Irene E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308699/
https://www.ncbi.nlm.nih.gov/pubmed/22431752
http://dx.doi.org/10.1083/jcb.201105101
_version_ 1782227446802677760
author Sarkar, Anjali A.
Zohn, Irene E.
author_facet Sarkar, Anjali A.
Zohn, Irene E.
author_sort Sarkar, Anjali A.
collection PubMed
description Hectd1 mutant mouse embryos exhibit the neural tube defect exencephaly associated with abnormal cranial mesenchyme. Cellular rearrangements in cranial mesenchyme are essential during neurulation for elevation of the neural folds. Here we investigate the molecular basis of the abnormal behavior of Hectd1 mutant cranial mesenchyme. We demonstrate that Hectd1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Extracellular Hsp90 enhances migration of multiple cell types. In mutant cranial mesenchyme cells, both secretion of Hsp90 and emigration of cells from cranial mesenchyme explants were enhanced. Importantly, we show that this enhanced emigration was highly dependent on the excess Hsp90 secreted from mutant cells. Together, our data set forth a model whereby increased secretion of Hsp90 in the cranial mesenchyme of Hectd1 mutants is responsible, at least in part, for the altered organization and behavior of these cells and provides a potential molecular mechanism underlying the neural tube defect.
format Online
Article
Text
id pubmed-3308699
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-33086992012-09-19 Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme Sarkar, Anjali A. Zohn, Irene E. J Cell Biol Research Articles Hectd1 mutant mouse embryos exhibit the neural tube defect exencephaly associated with abnormal cranial mesenchyme. Cellular rearrangements in cranial mesenchyme are essential during neurulation for elevation of the neural folds. Here we investigate the molecular basis of the abnormal behavior of Hectd1 mutant cranial mesenchyme. We demonstrate that Hectd1 is a functional ubiquitin ligase and that one of its substrates is Hsp90, a chaperone protein with both intra- and extracellular clients. Extracellular Hsp90 enhances migration of multiple cell types. In mutant cranial mesenchyme cells, both secretion of Hsp90 and emigration of cells from cranial mesenchyme explants were enhanced. Importantly, we show that this enhanced emigration was highly dependent on the excess Hsp90 secreted from mutant cells. Together, our data set forth a model whereby increased secretion of Hsp90 in the cranial mesenchyme of Hectd1 mutants is responsible, at least in part, for the altered organization and behavior of these cells and provides a potential molecular mechanism underlying the neural tube defect. The Rockefeller University Press 2012-03-19 /pmc/articles/PMC3308699/ /pubmed/22431752 http://dx.doi.org/10.1083/jcb.201105101 Text en © 2012 Sarkar and Zohn This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Research Articles
Sarkar, Anjali A.
Zohn, Irene E.
Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme
title Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme
title_full Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme
title_fullStr Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme
title_full_unstemmed Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme
title_short Hectd1 regulates intracellular localization and secretion of Hsp90 to control cellular behavior of the cranial mesenchyme
title_sort hectd1 regulates intracellular localization and secretion of hsp90 to control cellular behavior of the cranial mesenchyme
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3308699/
https://www.ncbi.nlm.nih.gov/pubmed/22431752
http://dx.doi.org/10.1083/jcb.201105101
work_keys_str_mv AT sarkaranjalia hectd1regulatesintracellularlocalizationandsecretionofhsp90tocontrolcellularbehaviorofthecranialmesenchyme
AT zohnirenee hectd1regulatesintracellularlocalizationandsecretionofhsp90tocontrolcellularbehaviorofthecranialmesenchyme