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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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Identification of an apical sorting determinant in the cytoplasmic tail of megalin

Tetsuro Takeda1, Hajime Yamazaki, Marilyn G Farquhar

  • 1Department of Cellular and Molecular Medicine, University of California, San Diego, La Jolla, California 92093, USA.

American Journal of Physiology. Cell Physiology
|January 10, 2003
PubMed

Insights

Researchers identified a novel apical sorting signal in the megalin protein

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Biochemistry

Background:

  • Megalin, a key endocytic receptor in kidney proximal tubules, reabsorbs filtered proteins.
  • Unlike other LDL receptor family members, megalin localizes to the apical plasma membrane of polarized epithelial cells.

Discussion:

  • Investigated megalin's apical sorting mechanism using deletion mutants and chimeric minireceptors in Madin-Darby canine kidney (MDCK) cells.
  • Assessed protein distribution via immunofluorescence and cell surface biotinylation.
  • Megalin and LRP minireceptors correctly localized to apical and basolateral membranes, respectively.

Key Insights:

  • The cytoplasmic tail (CT) of megalin contains critical information for apical sorting.
  • Amino acids 107-136 within the megalin-CT, including an NPXY-like motif, are essential for apical targeting.
  • Specific regions of the CT are also required for efficient endocytosis.

Outlook:

  • The megalin-CT harbors a previously unknown apical sorting determinant.
  • Evidence suggests the existence of specific cytoplasmic sorting machinery for certain apical transmembrane proteins in MDCK cells.

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