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LMP4 regulates Tbx5 protein subcellular localization and activity

The limb- and heart-specific Tbx5 transcription factor coexpresses with and directly binds to the novel PDZ-LIM domain protein, LMP4. LMP4 is distributed in the cytoplasm associated with the actin cytoskeleton. In the presence of LMP4, Tbx5 shuttles dynamically between the nucleus and cytoplasm and,...

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Autores principales: Camarata, Troy, Bimber, Benjamin, Kulisz, Andre, Chew, Teng-Leong, Yeung, Jennifer, Simon, Hans-Georg
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2006
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064230/
https://www.ncbi.nlm.nih.gov/pubmed/16880269
http://dx.doi.org/10.1083/jcb.200511109
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author Camarata, Troy
Bimber, Benjamin
Kulisz, Andre
Chew, Teng-Leong
Yeung, Jennifer
Simon, Hans-Georg
author_facet Camarata, Troy
Bimber, Benjamin
Kulisz, Andre
Chew, Teng-Leong
Yeung, Jennifer
Simon, Hans-Georg
author_sort Camarata, Troy
collection PubMed
description The limb- and heart-specific Tbx5 transcription factor coexpresses with and directly binds to the novel PDZ-LIM domain protein, LMP4. LMP4 is distributed in the cytoplasm associated with the actin cytoskeleton. In the presence of LMP4, Tbx5 shuttles dynamically between the nucleus and cytoplasm and, in a complex with LMP4, localizes to actin filaments. Nuclear and cytoplasmic Tbx5 distribution in developing chicken wings suggests the functional significance of the LMP4–Tbx5 interaction. In primary epicardial cells, we demonstrate that Tbx5 protein subcellular relocalization can be stimulated by external signals that induce cell differentiation. To test whether the relocalization from nuclear to cytoplasmic sites interferes with downstream gene expression, we used limb-specific Fgf10 and heart-specific Anf promoter-luciferase reporters and demonstrate that LMP4 acts as a repressor of Tbx5 activity. These studies reveal a previously unknown mechanism for Tbx transcription factor regulation in vertebrate limb and heart development and provide a better understanding of the molecular basis of hand/heart birth defects associated with Tbx5 mutations.
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spelling pubmed-20642302007-11-29 LMP4 regulates Tbx5 protein subcellular localization and activity Camarata, Troy Bimber, Benjamin Kulisz, Andre Chew, Teng-Leong Yeung, Jennifer Simon, Hans-Georg J Cell Biol Research Articles The limb- and heart-specific Tbx5 transcription factor coexpresses with and directly binds to the novel PDZ-LIM domain protein, LMP4. LMP4 is distributed in the cytoplasm associated with the actin cytoskeleton. In the presence of LMP4, Tbx5 shuttles dynamically between the nucleus and cytoplasm and, in a complex with LMP4, localizes to actin filaments. Nuclear and cytoplasmic Tbx5 distribution in developing chicken wings suggests the functional significance of the LMP4–Tbx5 interaction. In primary epicardial cells, we demonstrate that Tbx5 protein subcellular relocalization can be stimulated by external signals that induce cell differentiation. To test whether the relocalization from nuclear to cytoplasmic sites interferes with downstream gene expression, we used limb-specific Fgf10 and heart-specific Anf promoter-luciferase reporters and demonstrate that LMP4 acts as a repressor of Tbx5 activity. These studies reveal a previously unknown mechanism for Tbx transcription factor regulation in vertebrate limb and heart development and provide a better understanding of the molecular basis of hand/heart birth defects associated with Tbx5 mutations. The Rockefeller University Press 2006-07-31 /pmc/articles/PMC2064230/ /pubmed/16880269 http://dx.doi.org/10.1083/jcb.200511109 Text en Copyright © 2006, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Research Articles
Camarata, Troy
Bimber, Benjamin
Kulisz, Andre
Chew, Teng-Leong
Yeung, Jennifer
Simon, Hans-Georg
LMP4 regulates Tbx5 protein subcellular localization and activity
title LMP4 regulates Tbx5 protein subcellular localization and activity
title_full LMP4 regulates Tbx5 protein subcellular localization and activity
title_fullStr LMP4 regulates Tbx5 protein subcellular localization and activity
title_full_unstemmed LMP4 regulates Tbx5 protein subcellular localization and activity
title_short LMP4 regulates Tbx5 protein subcellular localization and activity
title_sort lmp4 regulates tbx5 protein subcellular localization and activity
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064230/
https://www.ncbi.nlm.nih.gov/pubmed/16880269
http://dx.doi.org/10.1083/jcb.200511109
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