Abstract
Cilia are highly specialized antennae-like cellular organelles. Inositol polyphosphate 5-phosphatase E (INPP5E) converts PI(4,5)P2 into PI4P and is required for proper ciliary function. Although Inpp5e mutations are associated with ciliopathies in humans and mice, the precise molecular role INPP5E plays in cilia remains unclear. Here, we report that Drosophila INPP5E (dINPP5E) regulates ciliary protein trafficking by controlling the phosphoinositide composition of ciliary membranes. Mutations in dInpp5e lead to hearing deficits due to the mislocalization of dTULP and mechanotransduction channels, Inactive and NOMPC, in chordotonal cilia. Both loss of dINPP5E and ectopic expression of the phosphatidylinositol-4-phosphate 5-kinase Skittles increase PI(4,5)P2 levels in the ciliary base. The fact that Skittles expression phenocopies the dInpp5e mutants confirms a central role for PI(4,5)P2 in the regulation of dTULP, Inactive, and NOMPC localization. These data suggest that the spatial localization and levels of PI(4,5)P2 in ciliary membranes are important regulators of ciliary trafficking and function. Park et al. report that Drosophila INPP5E regulates PI(4,5)P2 levels in the ciliary membrane. Loss of dInpp5e increases PI(4,5)P2 levels in the ciliary base. This, in turn, causes a ciliary accumulation of dTULP and consequent mislocalization of IAV and NOMPC.
| Original language | English |
|---|---|
| Pages (from-to) | 2808-2816 |
| Number of pages | 9 |
| Journal | Cell Reports |
| Volume | 13 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 2015 Dec 29 |
Bibliographical note
Funding Information:We thank M. Kernan for providing reagents and the Bloomington Stock Center and the Vienna Drosophila RNAi Center for providing fly stocks. The anti-α-tubulin monoclonal antibody was developed by J. Frankel and E.M. Nelsen, and the 21A6 and 22C10 monoclonals were developed by S. Benzer. All three were obtained from the Developmental Studies Hybridoma Bank, which was itself developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biology. This study was supported by the Bio & Medical Technology Development Program (no. 2012M3A9B2052524 to S.J.M.) and by the Kiturami Faculty Research Assistance Program of Yonsei University College of Medicine for 2013 (6-2013-0158 to C.H.K.) and the Brain Korea 21 PLUS Project for Medical Science.
Funding Information:
We thank M. Kernan for providing reagents and the Bloomington Stock Center and the Vienna Drosophila RNAi Center for providing fly stocks. The anti-α-tubulin monoclonal antibody was developed by J. Frankel and E.M. Nelsen, and the 21A6 and 22C10 monoclonals were developed by S. Benzer. All three were obtained from the Developmental Studies Hybridoma Bank, which was itself developed under the auspices of the NICHD and maintained by the University of Iowa, Department of Biology. This study was supported by the Bio & Medical Technology Development Program (no. 2012M3A9B2052524 to S.J.M.) and by the Kiturami Faculty Research Assistance Program of Yonsei University College of Medicine for 2013 (6-2013-0158 to C.H.K.) and the Brain Korea 21 PLUS Project for Medical Science.
Publisher Copyright:
© 2015 The Authors
All Science Journal Classification (ASJC) codes
- Biochemistry, Genetics and Molecular Biology(all)