Cargando…

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...

Descripción completa

Detalles Bibliográficos
Autores principales: Málaga-Trillo, Edward, Solis, Gonzalo P, Schrock, Yvonne, Geiss, Corinna, Luncz, Lydia, Thomanetz, Venus, Stuermer, Claudia A. O
Formato: Texto
Lenguaje:English
Publicado: Public Library of Science 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653553/
https://www.ncbi.nlm.nih.gov/pubmed/19278297
http://dx.doi.org/10.1371/journal.pbio.1000055
_version_ 1782165293581205504
author Málaga-Trillo, Edward
Solis, Gonzalo P
Schrock, Yvonne
Geiss, Corinna
Luncz, Lydia
Thomanetz, Venus
Stuermer, Claudia A. O
author_facet Málaga-Trillo, Edward
Solis, Gonzalo P
Schrock, Yvonne
Geiss, Corinna
Luncz, Lydia
Thomanetz, Venus
Stuermer, Claudia A. O
author_sort Málaga-Trillo, Edward
collection PubMed
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 Text
id pubmed-2653553
institution National Center for Biotechnology Information
language English
publishDate 2009
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-26535532009-03-10 Regulation of Embryonic Cell Adhesion by the Prion Protein Málaga-Trillo, Edward Solis, Gonzalo P Schrock, Yvonne Geiss, Corinna Luncz, Lydia Thomanetz, Venus Stuermer, Claudia A. O PLoS Biol Research Article 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. Public Library of Science 2009-03 2009-03-10 /pmc/articles/PMC2653553/ /pubmed/19278297 http://dx.doi.org/10.1371/journal.pbio.1000055 Text en © 2009 Málaga-Trillo et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Málaga-Trillo, Edward
Solis, Gonzalo P
Schrock, Yvonne
Geiss, Corinna
Luncz, Lydia
Thomanetz, Venus
Stuermer, Claudia A. O
Regulation of Embryonic Cell Adhesion by the Prion Protein
title 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_short Regulation of Embryonic Cell Adhesion by the Prion Protein
title_sort regulation of embryonic cell adhesion by the prion protein
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2653553/
https://www.ncbi.nlm.nih.gov/pubmed/19278297
http://dx.doi.org/10.1371/journal.pbio.1000055
work_keys_str_mv AT malagatrilloedward regulationofembryoniccelladhesionbytheprionprotein
AT solisgonzalop regulationofembryoniccelladhesionbytheprionprotein
AT schrockyvonne regulationofembryoniccelladhesionbytheprionprotein
AT geisscorinna regulationofembryoniccelladhesionbytheprionprotein
AT lunczlydia regulationofembryoniccelladhesionbytheprionprotein
AT thomanetzvenus regulationofembryoniccelladhesionbytheprionprotein
AT stuermerclaudiaao regulationofembryoniccelladhesionbytheprionprotein