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XB-ART-43161
J Biol Chem. June 17, 2011; 286 (24): 21239-53.

ERp29 regulates DeltaF508 and wild-type cystic fibrosis transmembrane conductance regulator (CFTR) trafficking to the plasma membrane in cystic fibrosis (CF) and non-CF epithelial cells.

Suaud L , Miller K , Alvey L , Yan W , Robay A , Kebler C , Kreindler JL , Guttentag S , Hubbard MJ , Rubenstein RC .


Abstract
Sodium 4-phenylbutyrate (4PBA) improves the intracellular trafficking of ΔF508-CFTR in cystic fibrosis (CF) epithelial cells. The underlying mechanism is uncertain, but 4PBA modulates the expression of some cytosolic molecular chaperones. To identify other 4PBA-regulated proteins that might regulate ΔF508-CFTR trafficking, we performed a differential display RT-PCR screen on IB3-1 CF bronchiolar epithelial cells exposed to 4PBA. One transcript up-regulated by 4PBA encoded ERp29, a luminal resident of the endoplasmic reticulum (ER) thought to be a novel molecular chaperone. We tested the hypothesis that ERp29 is a 4PBA-regulated ER chaperone that influences ΔF508-CFTR trafficking. ERp29 mRNA and protein expression was significantly increased (∼1.5-fold) in 4PBA-treated IB3-1 cells. In Xenopus oocytes, ERp29 overexpression increased the functional expression of both wild-type and ΔF508-CFTR over 3-fold and increased wild-type cystic fibrosis transmembrane conductance regulator (CFTR) plasma membrane expression. In CFBE41o- WT-CFTR cells, expression of and short circuit currents mediated by CFTR decreased upon depletion of ERp29 as did maturation of newly synthesized CFTR. In IB3-1 cells, ΔF508-CFTR co-immunoprecipitated with endogenous ERp29, and overexpression of ERp29 led to increased ΔF508-CFTR expression at the plasma membrane. These data suggest that ERp29 is a 4PBA-regulated ER chaperone that regulates WT-CFTR biogenesis and can promote ΔF508-CFTR trafficking in CF epithelial cells.

PubMed ID: 21525008
PMC ID: PMC3122184
Article link: J Biol Chem.
Grant support: K08 HL081080 NHLBI NIH HHS , K08 HL081080 NHLBI NIH HHS , K08 HL081080 NHLBI NIH HHS , K08 HL081080 NHLBI NIH HHS , K08 HL081080 NHLBI NIH HHS , K08 HL081080 NHLBI NIH HHS , R01 DK058046 NIDDK NIH HHS , R01 DK073185 NIDDK NIH HHS , R01 HL059959 NHLBI NIH HHS , R01 HL059959 NHLBI NIH HHS , R01 HL059959 NHLBI NIH HHS , R01 HL059959 NHLBI NIH HHS , R01 HL059959 NHLBI NIH HHS , R01 HL059959 NHLBI NIH HHS , T35 HD0744 NICHD NIH HHS , R01 DK058046-10 NIDDK NIH HHS , R01 DK058046-11 NIDDK NIH HHS

Genes referenced: cftr erp29
Antibodies referenced:
Morpholinos referenced:

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