Regulation of embryonic cell adhesion by the prion protein.

Prion proteins (PrPs) are key players in fatal neurodegenerative disorders, yet their physiological functions remain unclear, as PrP knockout mice develop rather normally. We report a strong PrP loss-of-function phenotype in zebrafish embryos, characterized by the loss of embryonic cell adhesion and...

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Autores principales:	Edward Málaga-Trillo, Gonzalo P Solis, Yvonne Schrock, Corinna Geiss, Lydia Luncz, Venus Thomanetz, Claudia A O Stuermer
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2009
Materias:	Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/a9a69c6eb6874bedb300ea793e98bf61
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spelling	oai:doaj.org-article:a9a69c6eb6874bedb300ea793e98bf612021-11-25T05:33:46ZRegulation of embryonic cell adhesion by the prion protein.1544-91731545-788510.1371/journal.pbio.1000055https://doaj.org/article/a9a69c6eb6874bedb300ea793e98bf612009-03-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/19278297/?tool=EBIhttps://doaj.org/toc/1544-9173https://doaj.org/toc/1545-7885Prion proteins (PrPs) are key players in fatal neurodegenerative disorders, yet their physiological functions remain unclear, as PrP knockout mice develop rather normally. We report a strong PrP loss-of-function phenotype in zebrafish embryos, characterized by the loss of embryonic cell adhesion and arrested gastrulation. Zebrafish and mouse PrP mRNAs can partially rescue this knockdown phenotype, indicating conserved PrP functions. Using zebrafish, mouse, and Drosophila cells, we show that PrP: (1) mediates Ca(+2)-independent homophilic cell adhesion and signaling; and (2) modulates Ca(+2)-dependent cell adhesion by regulating the delivery of E-cadherin to the plasma membrane. In vivo time-lapse analyses reveal that the arrested gastrulation in PrP knockdown embryos is due to deficient morphogenetic cell movements, which rely on E-cadherin-based adhesion. Cell-transplantation experiments indicate that the regulation of embryonic cell adhesion by PrP is cell-autonomous. Moreover, we find that the local accumulation of PrP at cell contact sites is concomitant with the activation of Src-related kinases, the recruitment of reggie/flotillin microdomains, and the reorganization of the actin cytoskeleton, consistent with a role of PrP in the modulation of cell adhesion via signaling. Altogether, our data uncover evolutionarily conserved roles of PrP in cell communication, which ultimately impinge on the stability of adherens cell junctions during embryonic development.Edward Málaga-TrilloGonzalo P SolisYvonne SchrockCorinna GeissLydia LunczVenus ThomanetzClaudia A O StuermerPublic Library of Science (PLoS)articleBiology (General)QH301-705.5ENPLoS Biology, Vol 7, Iss 3, p e55 (2009)
institution	DOAJ
collection	DOAJ
language	EN
topic	Biology (General) QH301-705.5
spellingShingle	Biology (General) QH301-705.5 Edward Málaga-Trillo Gonzalo P Solis Yvonne Schrock Corinna Geiss Lydia Luncz Venus Thomanetz Claudia A O Stuermer Regulation of embryonic cell adhesion by the prion protein.
description	Prion proteins (PrPs) are key players in fatal neurodegenerative disorders, yet their physiological functions remain unclear, as PrP knockout mice develop rather normally. We report a strong PrP loss-of-function phenotype in zebrafish embryos, characterized by the loss of embryonic cell adhesion and arrested gastrulation. Zebrafish and mouse PrP mRNAs can partially rescue this knockdown phenotype, indicating conserved PrP functions. Using zebrafish, mouse, and Drosophila cells, we show that PrP: (1) mediates Ca(+2)-independent homophilic cell adhesion and signaling; and (2) modulates Ca(+2)-dependent cell adhesion by regulating the delivery of E-cadherin to the plasma membrane. In vivo time-lapse analyses reveal that the arrested gastrulation in PrP knockdown embryos is due to deficient morphogenetic cell movements, which rely on E-cadherin-based adhesion. Cell-transplantation experiments indicate that the regulation of embryonic cell adhesion by PrP is cell-autonomous. Moreover, we find that the local accumulation of PrP at cell contact sites is concomitant with the activation of Src-related kinases, the recruitment of reggie/flotillin microdomains, and the reorganization of the actin cytoskeleton, consistent with a role of PrP in the modulation of cell adhesion via signaling. Altogether, our data uncover evolutionarily conserved roles of PrP in cell communication, which ultimately impinge on the stability of adherens cell junctions during embryonic development.
format	article
author	Edward Málaga-Trillo Gonzalo P Solis Yvonne Schrock Corinna Geiss Lydia Luncz Venus Thomanetz Claudia A O Stuermer
author_facet	Edward Málaga-Trillo Gonzalo P Solis Yvonne Schrock Corinna Geiss Lydia Luncz Venus Thomanetz Claudia A O Stuermer
author_sort	Edward Málaga-Trillo
title	Regulation of embryonic cell adhesion by the prion protein.
title_short	Regulation of embryonic cell adhesion by the prion protein.
title_full	Regulation of embryonic cell adhesion by the prion protein.
title_fullStr	Regulation of embryonic cell adhesion by the prion protein.
title_full_unstemmed	Regulation of embryonic cell adhesion by the prion protein.
title_sort	regulation of embryonic cell adhesion by the prion protein.
publisher	Public Library of Science (PLoS)
publishDate	2009
url	https://doaj.org/article/a9a69c6eb6874bedb300ea793e98bf61
work_keys_str_mv	AT edwardmalagatrillo regulationofembryoniccelladhesionbytheprionprotein AT gonzalopsolis regulationofembryoniccelladhesionbytheprionprotein AT yvonneschrock regulationofembryoniccelladhesionbytheprionprotein AT corinnageiss regulationofembryoniccelladhesionbytheprionprotein AT lydialuncz regulationofembryoniccelladhesionbytheprionprotein AT venusthomanetz regulationofembryoniccelladhesionbytheprionprotein AT claudiaaostuermer regulationofembryoniccelladhesionbytheprionprotein
_version_	1718414597424152576

Regulation of embryonic cell adhesion by the prion protein.

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