PrPC Undergoes Basal to Apical Transcytosis in Polarized Epithelial MDCK Cells

Alexander Arkhipenko1, Sylvie Syan1, Guiliana Soraya Victoria1

  • 1Unité de Trafic Membranaire et Pathogénèse, Institut Pasteur, 25-28 rue du docteur Roux, 75015, Paris, France.

Plos One
|July 9, 2016
PubMed

Insights

The cellular prion protein (PrP) undergoes transcytosis from the basolateral to apical membrane in polarized epithelial cells. This trafficking mechanism allows for segregation of full-length PrP and its fragments in distinct plasma membrane domains.

Area of Science:

  • Cell Biology
  • Neuroscience
  • Biochemistry

Background:

  • The cellular prion protein (PrPC) is a glycosylphosphatidylinositol (GPI)-anchored membrane protein with an undefined function.
  • Prion diseases are linked to the misfolded PrPSc isoform, but the normal function and trafficking of PrPC remain unclear.
  • PrP localization in polarized Madin-Darby canine kidney (MDCK) cells is controversial, and its trafficking mechanisms are not well understood.

Purpose of the Study:

  • To investigate the trafficking mechanisms of PrP in polarized epithelial cells.
  • To determine if PrP exhibits unique trafficking properties compared to other GPI-anchored proteins (GPI-APs).
  • To analyze PrP localization and segregation in both 2D and 3D cell culture models.

Main Methods:

  • Utilized MDCK cells cultured on filters to establish polarized epithelial monolayers.
  • Employed three-dimensional MDCK cyst cultures as a more physiologically relevant model of polarized epithelia.
  • Investigated the transcytosis and membrane domain segregation of PrP and its cleavage fragments.

Main Results:

  • PrP undergoes basolateral-to-apical transcytosis in fully polarized MDCK cells, a distinct pathway from other GPI-APs.
  • Full-length PrP and its cleavage fragments are segregated into different plasma membrane domains after transcytosis.
  • These segregation patterns were observed in both 2D filter cultures and 3D cyst models.

Conclusions:

  • PrP exhibits unique transcytosis and segregation mechanisms in polarized epithelial cells.
  • The distinct trafficking and localization of PrP and its fragments suggest specialized roles in epithelial function.
  • These findings provide new insights into the cell biology of PrP in polarized epithelia.

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