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The C. elegans Intestine As a Model for Intercellular Lumen Morphogenesis and In Vivo Polarized Membrane Biogenesis at the Single-cell Level: Labeling by Antibody Staining, RNAi Loss-of-function Analysis and Imaging
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CASK deletion in intestinal epithelia causes mislocalization of LIN7C and the DLG1/Scrib polarity complex without

Larissa Lozovatsky1, Nirmalee Abayasekara, Sorbarikor Piawah

  • 1Department of Pathology, Yale University School of Medicine, New Haven, CT 06520, USA.

Molecular Biology of the Cell
|September 4, 2009
PubMed

Insights

Calcium/calmodulin-dependent serine protein kinase (CASK) is not essential for intestinal epithelial polarity or homeostasis. Its absence does not affect epithelial differentiation or crypt-to-villus migration in mice.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Genetics

Background:

  • CASK (Calcium/calmodulin-dependent serine protein kinase) is a MAGUK family scaffolding protein.
  • It is the mammalian ortholog of Caenorhabditis elegans LIN2 and interacts with LIN7 and DLG1.
  • CASK localizes to basolateral membranes in polarized epithelia and plays a role in targeting EGFR.

Purpose of the Study:

  • To investigate the role of CASK in epithelial polarity and intestinal homeostasis.
  • To determine the necessity of CASK for the localization of DLG1 and LIN7C in the intestine.
  • To assess the impact of CASK deficiency on epithelial differentiation and crypt-to-villus migration.

Main Methods:

  • Generation of intestine-specific CASK knockout mice.
  • Immunofluorescence analysis of CASK-deficient intestinal and stomach tissues.
  • Assessment of epithelial polarity, differentiation, protein localization, and crypt-to-villus migration rates.

Main Results:

  • CASK is not required for epithelial polarity or differentiation in the mouse intestine.
  • CASK is necessary for the basolateral localization of DLG1 and LIN7C in the intestine, but not the stomach.
  • CASK deficiency does not affect the localization of LIN7A/B, EGFR, or ErbB-2, nor crypt-to-villus migration.

Conclusions:

  • CASK expression is not essential for maintaining epithelial polarity or intestinal homeostasis in vivo.
  • The basolateral localization of DLG1 is dependent on CASK in the intestine, but this is not critical for overall intestinal function.
  • CASK's role in protein localization appears to be tissue-specific within the gastrointestinal tract.

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