These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Basolateral sorting of transforming growth factor-alpha precursor in polarized epithelial cells: characterization of cytoplasmic domain determinants.
    Author: Dempsey PJ, Meise KS, Coffey RJ.
    Journal: Exp Cell Res; 2003 May 01; 285(2):159-74. PubMed ID: 12706112.
    Abstract:
    In polarized Madin-Darby canine kidney (MDCK) cells, newly synthesized transforming growth factor-alpha precursor (proTGFalpha) is directly sorted to the basolateral cell surface where it is sequentially cleaved and released into the basolateral conditioned medium (Dempsey, P.J., Coffey, R.J., J. Biol. Chem. 269 (1994) 16878-16889). In the present study, the role of the proTGFalpha cytoplasmic domain in basolateral sorting has been investigated using deletional and site-directed mutagenesis, as well as chimeric analyses of different TGFalpha constructs stably expressed in MDCK cells. The loss of polarized secretion of a proTGFalpha secretory mutant (TGFsec88) indicated that the proTGFalpha transmembrane and/or cytoplasmic domains contain essential basolateral sorting information. Using reporter chimeras with two apically sorted membrane proteins, p75 neurotrophin growth factor receptor and placental alkaline phosphatase, we show that the proTGFalpha cytoplasmic domain contains dominant basolateral sorting information. Analysis of proTGFalpha cytoplasmic domain truncation and internal deletion mutants, together with site-directed mutagenesis studies within the full-length proTGFalpha cytoplasmic domain, revealed redundant basolateral sorting motifs. Importantly, the C-terminal type I PDZ-binding motif was not required for basolateral sorting as determined by the integrity of basolateral sorting in deletion mutants lacking this motif. ProTGFalpha basolateral sorting may have important consequences for ligand presentation and spatial compartmentalization of epidermal growth factor receptor signaling networks in polarized epithelial cells.
    [Abstract] [Full Text] [Related] [New Search]