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Dopamine receptors reveal an essential role of IFT-B, KIF17, and Rab23 in delivering specific receptors to primary cilia

  1. Alison Leaf
  2. Mark Von Zastrow  Is a corresponding author
  1. University of California, San Francisco, United States
Research Article
  • Cited 32
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Cite this article as: eLife 2015;4:e06996 doi: 10.7554/eLife.06996

Abstract

Appropriate physiological signaling by primary cilia depends on the specific targeting of particular receptors to the ciliary membrane, but how this occurs remains poorly understood. Here we show that D1-type dopaminergic receptors are delivered to cilia from the extra-ciliary plasma membrane by a mechanism requiring the receptor cytoplasmic tail, the intraflagellar transport complex-B (IFT-B), and ciliary kinesin KIF17. This targeting mechanism critically depends on Rab23, a small GTP-binding protein that has important effects on physiological signaling from cilia but was not known previously to be essential for ciliary delivery of any cargo. Depleting Rab23 prevents dopamine receptors from accessing the ciliary membrane. Conversely, fusion of Rab23 to a non-ciliary receptor is sufficient to drive robust, nucleotide-dependent mis-localization to the ciliary membrane. Dopamine receptors thus reveal a previously unrecognized mechanism of ciliary receptor targeting and functional role of Rab23 in promoting this process.

Article and author information

Author details

  1. Alison Leaf

    Program in Cell Biology, University of California, San Francisco, San Francisco, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Mark Von Zastrow

    Program in Cell Biology, University of California, San Francisco, San Francisco, United States
    For correspondence
    Mark.VonZastrow@ucsf.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. W James Nelson, Stanford University, United States

Publication history

  1. Received: February 13, 2015
  2. Accepted: July 15, 2015
  3. Accepted Manuscript published: July 16, 2015 (version 1)
  4. Version of Record published: August 24, 2015 (version 2)

Copyright

© 2015, Leaf & Von Zastrow

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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