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Author Notes:

Correspondence to Gregory J. Pazour: gregory.pazour@umassmed.edu

Author contributions: W.J. Monis and G.J. Pazour conceived the project and designed experiments.

W.J. Monis performed all experimental research and data analysis.

V. Faundez contributed advice, mouse tissue, and other reagents.

W.J. Monis, V. Faundez, and G.J. Pazour wrote the manuscript.

We thank Dr. Jovenal San Agustin for assistance with histology and Drs. Maxence Nachury, Peter Jackson, Jagesh Shah, Esteban Dell'Angelica, and Stephen Doxsey for sharing reagents.

The authors declare no competing financial interests.

Subject:

Research Funding:

This work was supported by funding from the National Institutes of Health grants GM060992 and DK103632 to G.J. Pazour and GM077569 and NS088503 to V. Faundez.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Cell Biology
  • LYSOSOME-RELATED ORGANELLES
  • POLYCYSTIC KIDNEY-DISEASE
  • HERMANSKY-PUDLAK-SYNDROME
  • INTRAFLAGELLAR TRANSPORT PROTEIN
  • SUSCEPTIBILITY FACTOR DYSBINDIN
  • ROD OUTER SEGMENT
  • PLASMA-MEMBRANE
  • EXOCYST COMPLEX
  • SACCHAROMYCES-CEREVISIAE
  • HIPPOCAMPAL-FORMATION
  • Disease
  • Cilia

BLOC-1 is required for selective membrane protein trafficking from endosomes to primary cilia

Tools:

Journal Title:

Journal of Cell Biology

Volume:

Volume 216, Number 7

Publisher:

, Pages 2131-2150

Type of Work:

Article | Final Publisher PDF

Abstract:

Primary cilia perceive the extracellular environment through receptors localized in the ciliary membrane, but mechanisms directing specific proteins to this domain are poorly understood. To address this question, we knocked down proteins potentially important for ciliary membrane targeting and determined how this affects the ciliary trafficking of fibrocystin, polycystin-2, and smoothened. Our analysis showed that fibrocystin and polycystin-2 are dependent on IFT20, GMAP210, and the exocyst complex, while smoothened delivery is largely independent of these components. In addition, we found that polycystin-2, but not smoothened or fibrocystin, requires the biogenesis of lysosome-related organelles complex-1 (BLOC-1) for ciliary delivery. Consistent with the role of BLOC-1 in sorting from the endosome, we find that disrupting the recycling endosome reduces ciliary polycystin-2 and causes its accumulation in the recycling endosome. This is the first demonstration of a role for BLOC-1 in ciliary assembly and highlights the complexity of pathways taken to the cilium.

Copyright information:

© 2017 Monis et al.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License (http://creativecommons.org/licenses/by-nc-sa/4.0/).

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