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Curr Biol. 2010 Oct 26;20(20):1840-5. doi: 10.1016/j.cub.2010.09.012. Epub 2010 Oct 7.

Cse1l is a negative regulator of CFTR-dependent fluid secretion.

Author information

  • 1Department of Cell Biology, Duke University School of Medicine, Durham, NC 27710, USA. m.bagnat@cellbio.duke.edu

Erratum in

  • Curr Biol. 2010 Dec 7;20(23):2157.

Abstract

Transport of chloride through the cystic fibrosis transmembrane conductance regulator (CFTR) channel is a key step in regulating fluid secretion in vertebrates [1, 2]. Loss of CFTR function leads to cystic fibrosis [1, 3, 4], a disease that affects the lungs, pancreas, liver, intestine, and vas deferens. Conversely, uncontrolled activation of the channel leads to increased fluid secretion and plays a major role in several diseases and conditions including cholera [5, 6] and other secretory diarrheas [7] as well as polycystic kidney disease [8-10]. Understanding how CFTR activity is regulated in vivo has been limited by the lack of a genetic model. Here, we used a forward genetic approach in zebrafish to uncover CFTR regulators. We report the identification, isolation, and characterization of a mutation in the zebrafish cse1l gene that leads to the sudden and dramatic expansion of the gut tube. We show that this phenotype results from a rapid accumulation of fluid due to the uncontrolled activation of the CFTR channel. Analyses in zebrafish larvae and mammalian cells indicate that Cse1l is a negative regulator of CFTR-dependent fluid secretion. This work demonstrates the importance of fluid homeostasis in development and establishes the zebrafish as a much-needed model system to study CFTR regulation in vivo.

Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID:
20933420
[PubMed - indexed for MEDLINE]
PMCID:
PMC2963654
Free PMC Article

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