Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity

The Frizzled (Fz; called here Fz1) and Fz2 receptors have distinct signaling specificities activating either the canonical Wnt/β-catenin pathway or Fz/planar cell polarity (PCP) signaling in Drosophila. The regulation of signaling specificity remains largely obscure. We show that Fz1 and Fz2 have di...

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Main Authors:	Wu, Jun, Klein, Thomas J, Mlodzik, Marek
Format:	Online
Language:	English
Published:	Public Library of Science 2004
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC449784/

id	pubmed-449784
recordtype	oai_dc
spelling	pubmed-4497842004-07-13 Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity Wu, Jun Klein, Thomas J Mlodzik, Marek Research Article The Frizzled (Fz; called here Fz1) and Fz2 receptors have distinct signaling specificities activating either the canonical Wnt/β-catenin pathway or Fz/planar cell polarity (PCP) signaling in Drosophila. The regulation of signaling specificity remains largely obscure. We show that Fz1 and Fz2 have different subcellular localizations in imaginal disc epithelia, with Fz1 localizing preferentially to apical junctional complexes, and Fz2 being evenly distributed basolaterally. The subcellular localization difference directly contributes to the signaling specificity outcome. Whereas apical localization favors Fz/PCP signaling, it interferes with canonical Wnt/β-catenin signaling. Receptor localization is mediated by sequences in the cytoplasmic tail of Fz2 that appear to block apical accumulation. Based on these data, we propose that subcellular Fz localization, through the association with other membrane proteins, is a critical aspect in regulating the signaling specificity within the Wnt/Fz signaling pathways. Public Library of Science 2004-07 2004-07-13 /pmc/articles/PMC449784/ /pubmed/15252441 http://dx.doi.org/10.1371/journal.pbio.0020158 Text en Copyright: © 2004 Wu 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Wu, Jun Klein, Thomas J Mlodzik, Marek
spellingShingle	Wu, Jun Klein, Thomas J Mlodzik, Marek Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity
author_facet	Wu, Jun Klein, Thomas J Mlodzik, Marek
author_sort	Wu, Jun
title	Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity
title_short	Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity
title_full	Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity
title_fullStr	Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity
title_full_unstemmed	Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity
title_sort	subcellular localization of frizzled receptors, mediated by their cytoplasmic tails, regulates signaling pathway specificity
description	The Frizzled (Fz; called here Fz1) and Fz2 receptors have distinct signaling specificities activating either the canonical Wnt/β-catenin pathway or Fz/planar cell polarity (PCP) signaling in Drosophila. The regulation of signaling specificity remains largely obscure. We show that Fz1 and Fz2 have different subcellular localizations in imaginal disc epithelia, with Fz1 localizing preferentially to apical junctional complexes, and Fz2 being evenly distributed basolaterally. The subcellular localization difference directly contributes to the signaling specificity outcome. Whereas apical localization favors Fz/PCP signaling, it interferes with canonical Wnt/β-catenin signaling. Receptor localization is mediated by sequences in the cytoplasmic tail of Fz2 that appear to block apical accumulation. Based on these data, we propose that subcellular Fz localization, through the association with other membrane proteins, is a critical aspect in regulating the signaling specificity within the Wnt/Fz signaling pathways.
publisher	Public Library of Science
publishDate	2004
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC449784/
_version_	1611368944394829824

Subcellular Localization of Frizzled Receptors, Mediated by Their Cytoplasmic Tails, Regulates Signaling Pathway Specificity

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