A conserved LDL-receptor motif regulates corin and CD320 membrane targeting in polarized renal epithelial cells

Elife. 2020 Nov 2:9:e56059. doi: 10.7554/eLife.56059.

Abstract

Selective protein distribution on distinct plasma membranes is important for epithelial cell function. To date, how proteins are directed to specific epithelial cell surface is not fully understood. Here we report a conserved DSSDE motif in LDL-receptor (LDLR) modules of corin (a transmembrane serine protease) and CD320 (a receptor for vitamin B12 uptake), which regulates apical membrane targeting in renal epithelial cells. Altering this motif prevents specific apical corin and CD320 expression in polarized Madin-Darby canine kidney (MDCK) cells. Mechanistic studies indicate that this DSSDE motif participates in a Rab11a-dependent mechanism that specifies apical sorting. In MDCK cells, inhibition of Rab11a, but not Rab11b, expression leads to corin and CD320 expression on both apical and basolateral membranes. Together, our results reveal a novel molecular recognition mechanism that regulates LDLR module-containing proteins in their specific apical expression in polarized renal epithelial cells.

Keywords: CD320; Rab11a; apical expression; cell biology; corin; human; ldl receptor module.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / metabolism*
  • Cell Polarity
  • Dogs
  • Epithelial Cells / metabolism*
  • Gene Expression Regulation
  • HEK293 Cells / metabolism
  • Humans
  • Kidney / cytology
  • Kidney / metabolism*
  • Madin Darby Canine Kidney Cells / metabolism
  • Receptors, Cell Surface / metabolism*
  • Receptors, LDL / genetics
  • Receptors, LDL / metabolism*
  • Sequence Alignment
  • Serine Endopeptidases / metabolism*

Substances

  • Antigens, CD
  • CD320 protein, human
  • Receptors, Cell Surface
  • Receptors, LDL
  • CORIN protein, human
  • Serine Endopeptidases