The Rab8 GTPase selectively regulates AP-1B-dependent basolateral transport in polarized Madin-Darby canine kidney cells

Agnes Lee Ang, Heike Fölsch, Ulla Maija Koivisto, Marc Pypaert, Ira Mellman*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

180 Scopus citations

Abstract

The AP-1B clathrin adaptor complex plays a key role in the recognition and intracellular transport of many membrane proteins destined for the basolateral surface of epithelial cells. However, little is known about other components that act in conjunction with AP-1B. We found that the Rab8 GTPase is one such component. Expression of a constitutively activated GTP hydrolysis mutant selectively inhibited basolateral (but not apical) transport of newly synthesized membrane proteins. Moreover, the effects were limited to AP-1B-dependent basolateral cargo; basolateral transport of proteins containing dileucine targeting motifs that do not interact with AP-1B were targeted normally despite overexpression of mutant Rab8. Similar results were obtained for a dominant-negative allele of the Rho GTPase Cdc42, previously implicated in basolateral transport but now shown to be selective for the AP-1B pathway. Rab8-GFP was localized to membranes in theTGN-recycling endosome, together with AP-1B complexes and the closely related but ubiquitously expressed AP-1A complex. However, expression of active Rab8 caused a selective dissociation of AP-1B complexes, reflecting the specificity of Rab8 for AP-1 B-dependent transport.

Original languageEnglish (US)
Pages (from-to)339-350
Number of pages12
JournalJournal of Cell Biology
Volume163
Issue number2
DOIs
StatePublished - Oct 27 2003

Keywords

  • AP-1
  • MDCK
  • Polarity
  • Rab8
  • Sorting

ASJC Scopus subject areas

  • Cell Biology

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