PDE6δ-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity

Nature Communications

Volumn 7, Issue , 2016, Pages

  Fansa, Eyad Kalawy ^a   Kösling, Stefanie Kristine ^a   Zent, Eldar ^a   Wittinghofer, Alfred ^a   Ismail, Shehab ^b  

^a MAX PLANCK INSTITUTE OF MOLECULAR PHYSIOLOGY   (Germany)

^b BEATSON INSTITUTE FOR CANCER RESEARCH   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ARL2 PROTEIN; ARL3 PROTEIN; CYSTEINE; INOSITOL POLYPHOSPHATE 5' PHOSPHATASE E; PHOSPHODIESTERASE 6 DELTA; PHOSPHODIESTERASE VI; REGULATOR PROTEIN; RHEB PROTEIN; SYNAPTOJANIN; UNCLASSIFIED DRUG; ADENOSINE DIPHOSPHATE RIBOSYLATION FACTOR; ARL3 PROTEIN, MOUSE; GREEN FLUORESCENT PROTEIN; GUANOSINE TRIPHOSPHATE; INOSITOL-POLYPHOSPHATE 5-PHOSPHATASE; MONOMERIC GUANINE NUCLEOTIDE BINDING PROTEIN; MUTANT PROTEIN; NEUROPEPTIDE; PHOSPHATASE; PROTEIN BINDING; RHEB PROTEIN, MOUSE; SIGNAL PEPTIDE;

ENRICHMENT; ENZYME ACTIVITY; MUTATION; PROTEIN; SIGNAL;

AMINO TERMINAL SEQUENCE; ANIMAL CELL; ARTICLE; BINDING AFFINITY; CONTROLLED STUDY; EUKARYOTIC FLAGELLUM; FARNESYLATION; MOUSE; MUCOCILIARY TRANSPORT; MUTATION; NONHUMAN; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PROTEIN INTERACTION; PROTEIN TARGETING; SIGNAL TRANSDUCTION; ANIMAL; BIOLOGICAL MODEL; CELL LINE; CHEMISTRY; FLUORESCENCE POLARIZATION; KINETICS; METABOLISM; PROTEIN PRENYLATION; PROTEIN SECONDARY STRUCTURE; PROTEIN TRANSPORT;

ADP-RIBOSYLATION FACTORS; ANIMALS; CELL LINE; CILIA; CYCLIC NUCLEOTIDE PHOSPHODIESTERASES, TYPE 6; FLUORESCENCE POLARIZATION; GREEN FLUORESCENT PROTEINS; GUANOSINE TRIPHOSPHATE; KINETICS; MICE; MODELS, BIOLOGICAL; MONOMERIC GTP-BINDING PROTEINS; MUTANT PROTEINS; NEUROPEPTIDES; PHOSPHORIC MONOESTER HYDROLASES; PROTEIN BINDING; PROTEIN PRENYLATION; PROTEIN SORTING SIGNALS; PROTEIN STRUCTURE, SECONDARY; PROTEIN TRANSPORT;

EID: 84964325372     PISSN: None     EISSN: 20411723     Source Type: Journal    
DOI: 10.1038/ncomms11366     Document Type: Article

References (44)

1. Badano, J. L., Mitsuma, N., Beales, P. L. and Katsanis, N. The ciliopathies: an emerging class of human genetic disorders. Annu. Rev. Genomics Hum. Genet. 7, 125-148 (2006).
2. Novarino, G., Akizu, N. and Gleeson, J. G. Modeling human disease in humans: the ciliopathies. Cell 147, 70-79 (2011).
3. Emmer, B. T., Maric, D. and Engman, D. M. Molecular mechanisms of protein and lipid targeting to ciliary membranes. J. Cell Sci. 123, 529-536 (2010).
4. Tyler, K. M. et al. Flagellar membrane localization via association with lipid rafts. J. Cell Sci. 122, 859-866 (2009).
5. Nozawa, Y. I., Lin, C. and Chuang, P. T. Hedgehog signaling from the primary cilium to the nucleus: an emerging picture of ciliary localization, trafficking and transduction. Curr. Opin. Genet. Dev. 23, 429-437 (2013).
6. Goetz, S. C., Ocbina, P. J. and Anderson, K. V. The primary cilium as a Hedgehog signal transduction machine. Methods Cell Biol. 94, 199-222 (2009).
7. Gillespie, P. G., Prusti, R. K., Apel, E. D. and Beavo, J. A. A soluble form of bovine rod photoreceptor phosphodiesterase has a novel 15-kDa subunit. J. Biol. Chem. 264, 12187-12193 (1989).
8. Florio, S. K., Prusti, R. K. and Beavo, J. A. Solubilization of membrane-bound rod phosphodiesterase by the rod phosphodiesterase recombinant delta subunit. J. Biol. Chem. 271, 24036-24047 (1996).
9. Zhang, H. et al. Photoreceptor cGMP phosphodiesterase delta subunit (PDEdelta) functions as a prenyl-binding protein. J. Biol. Chem. 279, 407-413 (2004).
10. Hanzal-Bayer, M., Renault, L., Roversi, P., Wittinghofer, A. and Hillig, R. C. The complex of Arl2-GTP and PDE delta: from structure to function. EMBO J. 21, 2095-2106 (2002).
11. Nancy, V., Callebaut, I., El Marjou, A. and de Gunzburg, J. The delta subunit of retinal rod cGMP phosphodiesterase regulates the membrane association of Ras and Rap GTPases. J. Biol. Chem. 277, 15076-15084 (2002).
12. Chen, Y. X. et al. Synthesis of the Rheb and K-Ras4B GTPases. Angew Chem. Int. Ed. Engl. 49, 6090-6095 (2010).
13. Ismail, S. A. et al. Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo. Nat. Chem. Biol. 7, 942-949 (2011).
14. Zhang, H., Constantine, R., Frederick, J. M. and Baehr, W. The prenyl-binding protein PrBP/delta: a chaperone participating in intracellular trafficking. Vision. Res. 75, 19-25 (2012).
15. Schmick, M. et al. KRas localizes to the plasma membrane by spatial cycles of solubilization, trapping and vesicular transport. Cell 157, 459-471 (2014).
16. Chandra, A. et al. The GDI-like solubilizing factor PDEdelta sustains the spatial organization and signalling of Ras family proteins. Nat. Cell Biol. 14, 148-158 (2012).
17. Zimmermann, G. et al. Small molecule inhibition of the KRAS-PDEdelta interaction impairs oncogenic KRAS signalling. Nature 497, 638-642 (2013).
18. Jacoby, M. et al. INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse. Nat. Genet. 41, 1027-1031 (2009).
19. Bielas, S. L. et al. Mutations in INPP5E, encoding inositol polyphosphate-5- phosphatase E, link phosphatidyl inositol signaling to the ciliopathies. Nat. Genet. 41, 1032-1036 (2009).
20. Travaglini, L. et al. Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders. Eur. J. Hum. Genet. 21, 1074-1078 (2013).
21. Pirruccello, M. and De Camilli, P. Inositol 5-phosphatases: insights from the Lowe syndrome protein OCRL. Trends Biochem. Sci. 37, 134-143 (2012).
22. Conduit, S. E., Dyson, J. M. and Mitchell, C. A. Inositol polyphosphate 5- phosphatases; new players in the regulation of cilia and ciliopathies. FEBS Lett. 586, 2846-2857 (2012).
23. De Smedt, F., Boom, A., Pesesse, X., Schiffmann, S. N. and Erneux, C. Post-translational modification of human brain type I inositol-1,4,5- trisphosphate 5-phosphatase by farnesylation. J. Biol. Chem. 271, 10419-10424 (1996).
24. Hampshire, D. J. et al. MORM syndrome (mental retardation, truncal obesity, retinal dystrophy and micropenis), a new autosomal recessive disorder, links to 9q34. Eur. J. Hum. Genet. 14, 543-548 (2006).
25. Thomas, S. et al. A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium. Hum. Mutat. 35, 137-146 (2014).
26. Humbert, M. C. et al. ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting. Proc. Natl Acad. Sci. USA 109, 19691-19696 (2012).
27. Zhang, H. et al. Mistrafficking of prenylated proteins causes retinitis pigmentosa 2. FASEB J. 29, 932-942 (2014).
28. Zhang, H. et al. Deletion of PrBP/delta impedes transport of GRK1 and PDE6 catalytic subunits to photoreceptor outer segments. Proc. Natl Acad. Sci. USA 104, 8857-8862 (2007).
29. Watzlich, D. et al. The interplay between RPGR, PDEdelta and Arl2/3 regulate the ciliary targeting of farnesylated cargo. EMBO. Rep. 14, 465-472 (2013).
30. Ismail, S. A. et al. Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119. EMBO J. 31, 4085-4094 (2012).
31. Nachury, M. V., Seeley, E. S. and Jin, H. Trafficking to the ciliary membrane: how to get across the periciliary diffusion barrier? Annu. Rev. Cell Dev. Biol. 26, 59-87 (2010).
32. Hsiao, Y. C., Tuz, K. and Ferland, R. J. Trafficking in and to the primary cilium. Cilia 1, 4 (2012).
33. Garcia-Gonzalo, F. R. and Reiter, J. F. Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access. J. Cell Biol. 197, 697-709 (2012).
34. Wright, K. J. et al. An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev. 25, 2347-2360 (2011).
35. Cheeseman, I. M. and Desai, A. A combined approach for the localization and tandem affinity purification of protein complexes from metazoans. Sci. STKE 2005, pl1 (2005).
36. Buerger, C., DeVries, B. and Stambolic, V. Localization of Rheb to the endomembrane is critical for its signaling function. Biochem. Biophys. Res. Commun. 344, 869-880 (2006).
37. Zhou, C., Cunningham, L., Marcus, A. I., Li, Y. and Kahn, R. A. Arl2 and Arl3 regulate different microtubule-dependent processes. Mol. Biol. Cell 17, 2476-2487 (2006).
38. Veltel, S., Kravchenko, A., Ismail, S. and Wittinghofer, A. Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3-effector-GAP complex. FEBS Lett. 582, 2501-2507 (2008).
39. Roehrl, M. H., Wang, J. Y. and Wagner, G. A general framework for development and data analysis of competitive high-throughput screens for small-molecule inhibitors of protein-protein interactions by fluorescence polarization. Biochemistry 43, 16056-16066 (2004).
40. Gotthardt, K. et al. A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins. Elife 4, e11859 (2015).
41. Evans, R. J. et al. The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the golgi and the primary cilium. Hum. Mol. Genet. 19, 1358-1367 (2010).
42. Hurd, T. et al. The retinitis pigmentosa protein RP2 interacts with polycystin 2 and regulates cilia-mediated vertebrate development. Hum. Mol. Genet. 19, 4330-4344 (2010).
43. Torres, J. Z., Miller, J. J. and Jackson, P. K. High-throughput generation of tagged stable cell lines for proteomic analysis. Proteomics 9, 2888-2891 (2009).
44. Sang, L. et al. Mapping the NPHP-JBTS-MKS protein network reveals ciliopathy disease genes and pathways. Cell 145, 513-528 (2011).