CLMP is essential for intestinal development, but does not play a key role in cellular processes involved in intestinal epithelial development

PLoS One. 2013;8(2):e54649. doi: 10.1371/journal.pone.0054649. Epub 2013 Feb 27.

Abstract

Loss-of-function mutations in CLMP have been found in patients with Congenital Short Bowel Syndrome (CSBS), suggesting that its encoded protein plays a major role in intestinal development. CLMP is a membrane protein that co-localizes with tight junction proteins, but its function is largely unknown. We expressed wild-type (WT)-CLMP and a mutant-CLMP (associated with CSBS) in human intestinal epithelial T84 cells that, as we show here, do not produce endogenous CLMP. We investigated the effects of WT-CLMP and mutant-CLMP proteins on key cellular processes that are important for intestinal epithelial development, including migration, proliferation, viability and transepithelial resistance. Our data showed that expression of WT-CLMP or mutant-CLMP does not affect any of these processes. Moreover, our aggregation assays in CHO cells show that CLMP does not act as a strong adhesion molecule. Thus, our data suggest that, in the in vitro model systems we used, the key processes involved in intestinal epithelial development appear to be unaffected by WT-CLMP or mutant-CLMP. Further research is needed to determine the role of CLMP in the development of the intestine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CHO Cells
  • Cell Adhesion Molecules / metabolism
  • Cell Aggregation
  • Cell Movement
  • Cell Proliferation
  • Cell Survival
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein / metabolism*
  • Cricetinae
  • Cricetulus
  • Electric Impedance
  • Epithelial Cells / cytology*
  • Epithelial Cells / metabolism*
  • Epithelium / growth & development*
  • Epithelium / metabolism
  • Humans
  • Intestines / growth & development*
  • Mutant Proteins / metabolism
  • Transduction, Genetic

Substances

  • CLMP protein, human
  • Cell Adhesion Molecules
  • Coxsackie and Adenovirus Receptor-Like Membrane Protein
  • Mutant Proteins

Grants and funding

This study was financially supported by the Junior Scientific Masterclass (University of Groningen) and the J.K. de Cockstichting. The funders had no role in study desing, data collection and analysis, decision to publish, or preparation of the manuscript.