Rab13 Regulates Membrane Trafficking Between TGN and Recycling Endosomes in Polarized Epithelial Cells

J Cell Biol. 2008 Sep 8;182(5):845-53. doi: 10.1083/jcb.200802176.

Abstract

To maintain polarity, epithelial cells continuously sort transmembrane proteins to the apical or basolateral membrane domains during biosynthetic delivery or after internalization. During biosynthetic delivery, some cargo proteins move from the trans-Golgi network (TGN) into recycling endosomes (RE) before being delivered to the plasma membrane. However, proteins that regulate this transport step remained elusive. In this study, we show that Rab13 partially colocalizes with TGN38 at the TGN and transferrin receptors in RE. Knockdown of Rab13 with short hairpin RNA in human bronchial epithelial cells or overexpression of dominant-active or dominant-negative alleles of Rab13 in Madin-Darby canine kidney cells disrupts TGN38/46 localization at the TGN. Moreover, overexpression of Rab13 mutant alleles inhibits surface arrival of proteins that move through RE during biosynthetic delivery (vesicular stomatitis virus glycoprotein [VSVG], A-VSVG, and LDLR-CT27). Importantly, proteins using a direct route from the TGN to the plasma membrane are not affected. Thus, Rab13 appears to regulate membrane trafficking between TGN and RE.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autoantigens / metabolism
  • Cell Polarity
  • Cells, Cultured
  • Dogs
  • Endosomes / metabolism*
  • Epithelial Cells / metabolism*
  • Golgi Apparatus / metabolism*
  • Humans
  • Membrane Glycoproteins / analysis
  • Membrane Glycoproteins / metabolism
  • Membrane Proteins / metabolism
  • Mutation
  • Protein Transport / physiology
  • Receptors, Transferrin / analysis
  • Receptors, Transferrin / metabolism
  • Viral Envelope Proteins / metabolism
  • rab GTP-Binding Proteins / analysis
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / physiology*

Substances

  • Autoantigens
  • G protein, vesicular stomatitis virus
  • Golgin subfamily A member 2
  • Membrane Glycoproteins
  • Membrane Proteins
  • Receptors, Transferrin
  • TGOLN2 protein, human
  • Viral Envelope Proteins
  • RAB13 protein, human
  • rab GTP-Binding Proteins