• Register
X
Forgot Password

If you have forgotten your password you can enter your email here and get a temporary password sent to your email.

X

Leaving Community

Are you sure you want to leave this community? Leaving the community will revoke any permissions you have been granted in this community.

No
Yes

The deubiquitinating enzyme USP10 regulates the endocytic recycling of CFTR in airway epithelial cells.

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) is a cyclic AMP-regulated chloride channel that plays an important role in regulating the volume of the lung airway surface liquid, and thereby mucociliary clearance and elimination of pathogens from the lung. In epithelial cells, cell surface CFTR abundance is determined in part by regulating both CFTR endocytosis from the apical plasma membrane and recycling back to the plasma membrane. We recently reported, using an activity-based chemical screen to identify active deubiquitinating enzymes (DUBs) in human airway epithelial cells, that Ubiquitin Specific Protease-10 (USP10) is located and active in the early endosomal compartment and regulates the deubiquitination of CFTR and thereby promotes its endocytic recycling. siRNA-mediated knockdown of USP10 increased the multi-ubiquitination and lysosomal degradation of CFTR and decreased the endocytic recycling and the half-life of CFTR in the apical membrane, as well as CFTR-mediated chloride secretion. Overexpression of wild-type USP10 reduced CFTR multi-ubiquitination and degradation, while overexpression of a dominant-negative USP10 promoted increased multi-ubiquitination and lysosomal degradation of CFTR. In the current study, we show localization and activity of USP10 in the early endosomal compartment of primary bronchial epithelial cells, as well as an interaction between CFTR and USP10 in this compartment. These studies demonstrate a novel function for USP10 in facilitating the deubiquitination of CFTR in early endosomes, thereby enhancing the endocytic recycling and cell surface expression of CFTR.

Pubmed ID: 20215869

Authors

  • Bomberger JM
  • Barnaby RL
  • Stanton BA

Journal

Channels (Austin, Tex.)

Publication Data

April 21, 2011

Associated Grants

  • Agency: NHLBI NIH HHS, Id: 2R01HL074175
  • Agency: NIDDK NIH HHS, Id: 5R01DK45581
  • Agency: NIDDK NIH HHS, Id: 5T32DK007301
  • Agency: NHLBI NIH HHS, Id: K99 HL098342
  • Agency: NIGMS NIH HHS, Id: P20 GM103413
  • Agency: NHLBI NIH HHS, Id: R00 HL098342
  • Agency: NHLBI NIH HHS, Id: R01 HL074175

Mesh Terms

  • Bronchi
  • Cell Membrane
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Endocytosis
  • Endopeptidases
  • Endosomes
  • Epithelial Cells
  • Epithelium
  • Humans
  • Protein Transport
  • Ubiquitin Thiolesterase
  • Ubiquitination