Basolateral delivery of the type i transforming growth factor beta receptor is mediated by a dominant-acting cytoplasmic motif

Xueqian Yin, Jeong Han Kang, Mahefatiana Andrianifahanana, Youli Wang, Mi Yeon Jung, Danielle M. Hernandez, Edward B. Leof

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)2701-2711
Number of pages11
JournalMolecular Biology of the Cell
Volume28
Issue number20
DOIs
Publication statusPublished - Oct 1 2017

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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