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

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

  • Dev Cell. 2014 Nov 10;31(3):265-278. doi: 10.1016/j.devcel.2014.09.004.
Gerald M Liew 1,  Fan Ye 2,  Andrew R Nager 2,  J Patrick Murphy 3,  Jaclyn S Lee 2,  Mike Aguiar 3,  David K Breslow 2,  Steven P Gygi 3,  Maxence V Nachury 4
Affiliations

Affiliations

  • 1 Department 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.
  • 2 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA.
  • 3 Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
  • 4 Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305, USA. Electronic address: [email protected].
PMID: 25443296 DOI: 10.1016/j.devcel.2014.09.004
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.

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