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Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif
Delivery of biomolecules to the correct subcellular locales is critical for proper physiological function. To that end, we have previously determined that type I and II transforming growth factor beta (TGF-β) receptors (TβRI and TβRII, respectively) localize to the basolateral domain in polarized ep...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620377/ https://www.ncbi.nlm.nih.gov/pubmed/28768825 http://dx.doi.org/10.1091/mbc.E17-05-0334 |
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author | Yin, Xueqian Kang, Jeong-Han Andrianifahanana, Mahefatiana Wang, Youli Jung, Mi-Yeon Hernandez, Danielle M. Leof, Edward B. |
author_facet | Yin, Xueqian Kang, Jeong-Han Andrianifahanana, Mahefatiana Wang, Youli Jung, Mi-Yeon Hernandez, Danielle M. Leof, Edward B. |
author_sort | Yin, Xueqian |
collection | PubMed |
description | Delivery of biomolecules to the correct subcellular locales is critical for proper physiological function. To that end, we have previously determined that type I and II transforming growth factor beta (TGF-β) receptors (TβRI and TβRII, respectively) localize to the basolateral domain in polarized epithelia. While TβRII targeting was shown to be regulated by sequences between amino acids 529 and 538, the analogous region(s) within TβRI is unknown. To address that question, sequential cytoplasmic TβRI truncations and point mutations identified a targeting motif between residues 158 and 163 (VxxEED) required for basolateral TβRI expression. Further studies documented that receptor internalization, down-regulation, direct recycling, or Smad signaling were unaffected by motif mutations that caused TβRI mislocalization. However, inclusion of amino acids 148–217 containing the targeting motif was able to direct basolateral expression of the apically sorted nerve growth factor receptor (NGFR, p75; extracellular and transmembrane regions) in a dominant manner. Finally, coexpression of apically targeted type I and type II TGF-β receptors mediated Smad3 signaling from the apical membrane of polarized epithelial cells. These findings demonstrate that the absence of apical TGF-β signaling in normal epithelia is primarily a reflection of domain-specific receptor expression and not an inability to couple with the signaling machinery. |
format | Online Article Text |
id | pubmed-5620377 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-56203772017-12-16 Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif Yin, Xueqian Kang, Jeong-Han Andrianifahanana, Mahefatiana Wang, Youli Jung, Mi-Yeon Hernandez, Danielle M. Leof, Edward B. Mol Biol Cell Articles Delivery of biomolecules to the correct subcellular locales is critical for proper physiological function. To that end, we have previously determined that type I and II transforming growth factor beta (TGF-β) receptors (TβRI and TβRII, respectively) localize to the basolateral domain in polarized epithelia. While TβRII targeting was shown to be regulated by sequences between amino acids 529 and 538, the analogous region(s) within TβRI is unknown. To address that question, sequential cytoplasmic TβRI truncations and point mutations identified a targeting motif between residues 158 and 163 (VxxEED) required for basolateral TβRI expression. Further studies documented that receptor internalization, down-regulation, direct recycling, or Smad signaling were unaffected by motif mutations that caused TβRI mislocalization. However, inclusion of amino acids 148–217 containing the targeting motif was able to direct basolateral expression of the apically sorted nerve growth factor receptor (NGFR, p75; extracellular and transmembrane regions) in a dominant manner. Finally, coexpression of apically targeted type I and type II TGF-β receptors mediated Smad3 signaling from the apical membrane of polarized epithelial cells. These findings demonstrate that the absence of apical TGF-β signaling in normal epithelia is primarily a reflection of domain-specific receptor expression and not an inability to couple with the signaling machinery. The American Society for Cell Biology 2017-10-01 /pmc/articles/PMC5620377/ /pubmed/28768825 http://dx.doi.org/10.1091/mbc.E17-05-0334 Text en © 2017 Yin et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology. |
spellingShingle | Articles Yin, Xueqian Kang, Jeong-Han Andrianifahanana, Mahefatiana Wang, Youli Jung, Mi-Yeon Hernandez, Danielle M. Leof, Edward B. Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif |
title | Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif |
title_full | Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif |
title_fullStr | Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif |
title_full_unstemmed | Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif |
title_short | Basolateral delivery of the type I transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif |
title_sort | basolateral delivery of the type i transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620377/ https://www.ncbi.nlm.nih.gov/pubmed/28768825 http://dx.doi.org/10.1091/mbc.E17-05-0334 |
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