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Dev Cell. 2014 Nov 10;31(3):265-78. doi: 10.1016/j.devcel.2014.09.004. Epub 2014 Oct 30.

The intraflagellar transport protein IFT27 promotes BBSome exit from cilia through the GTPase ARL6/BBS3.

Author information

  • 1Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA; Department of Biochemistry, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 2Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 3Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • 4Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: nachury@stanford.edu.

Abstract

The sorting of signaling receptors into and out of cilia relies on the BBSome, a complex of Bardet-Biedl syndrome (BBS) proteins, and on the intraflagellar transport (IFT) machinery. GTP loading onto the Arf-like GTPase ARL6/BBS3 drives assembly of a membrane-apposed BBSome coat that promotes cargo entry into cilia, yet how and where ARL6 is activated remains elusive. Here, we show that the Rab-like GTPase IFT27/RABL4, a known component of IFT complex B, promotes the exit of BBSome and associated cargoes from cilia. Unbiased proteomics and biochemical reconstitution assays show that, upon disengagement from the rest of IFT-B, IFT27 directly interacts with the nucleotide-free form of ARL6. Furthermore, IFT27 prevents aggregation of nucleotide-free ARL6 in solution. Thus, we propose that IFT27 separates from IFT-B inside cilia to promote ARL6 activation, BBSome coat assembly, and subsequent ciliary exit, mirroring the process by which BBSome mediates cargo entry into cilia.

PMID:
25443296
PMCID:
PMC4255629
DOI:
10.1016/j.devcel.2014.09.004
[PubMed - indexed for MEDLINE]
Free PMC Article
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