ARL3, a small GTPase with a functionally conserved role in primary cilia and immune synapses

References

• Nachury MV, Seeley ES, Jin H. Trafficking to the ciliary membrane: how to get across the periciliary diffusion barrier? Annu Rev Cell Dev Biol. 2010;26:59–87.
   PubMed Web of Science ®Google Scholar
• Garcia-Gonzalo FR, Reiter JF. Scoring a backstage pass: mechanisms of ciliogenesis and ciliary access. J Cell Biol. 2012;197(6):697–709.
   PubMed Web of Science ®Google Scholar
• Nachury MV, Mick DU. Establishing and regulating the composition of cilia for signal transduction. Nat Rev Mol Cell Biol. 2019;20(7):389–405.
   PubMed Web of Science ®Google Scholar
• Lin YC, Niewiadomski P, Lin B, et al. Chemically inducible diffusion trap at cilia reveals molecular sieve-like barrier. Nat Chem Biol. 2013;9(7):437–443.
   PubMed Web of Science ®Google Scholar
• Wright KJ, Baye LM, Olivier-Mason A, et al. An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium. Genes Dev. 2011;25(22):2347–2360.
   PubMed Web of Science ®Google Scholar
• Ismail SA, Chen YX, Miertzschke M, et al. Structural basis for Arl3-specific release of myristoylated ciliary cargo from UNC119. Embo J. 2012;31(20):4085–4094.
   PubMed Web of Science ®Google Scholar
• Gotthardt K, Lokaj M, Koerner C, et al. A G-protein activation cascade from Arl13B to Arl3 and implications for ciliary targeting of lipidated proteins. eLife. 2015;4:e11859.
   Web of Science ®Google Scholar
• Strom SP, Clark MJ, Martinez A, et al. De novo occurrence of a variant in ARL3 and apparent autosomal dominant transmission of retinitis pigmentosa. PLoS One. 2016;11(3):e0150944.
   PubMed Web of Science ®Google Scholar
• Holtan JP, Teigen K, Aukrust I, et al. Dominant ARL3-related retinitis pigmentosa. Ophthalmic Genet. 2019;40(2):124–128.
   PubMed Web of Science ®Google Scholar
• Alkanderi S, Molinari E, Shaheen R, et al. ARL3 mutations cause Joubert syndrome by disrupting ciliary protein composition. Am J Hum Genet. 2018;103(4):612–620.
   PubMed Web of Science ®Google Scholar
• Cassioli C, Baldari CT. A ciliary view of the immunological synapse. Cells. 2019;8(8):789.
   PubMed Web of Science ®Google Scholar
• Gawden-Bone CM, Griffiths GM. Phospholipids: pulling back the actin curtain for granule delivery to the immune synapse. Front Immunol. 2019;10:700.
   PubMed Web of Science ®Google Scholar
• Stephen LA, ElMaghloob Y, McIlwraith MJ, et al. The ciliary machinery is repurposed for T cell immune synapse trafficking of LCK. Dev Cell. 2018;47(1):122–32.e4.
   PubMed Web of Science ®Google Scholar
• Reiter JF, Leroux MR. Genes and molecular pathways underpinning ciliopathies. Nat Rev Mol Cell Biol. 2017;18(9):533–547.
   PubMed Web of Science ®Google Scholar
• Berbari NF, O’Connor AK, Haycraft CJ, et al. The primary cilium as a complex signaling center. Curr Biol. 2009;19(13):R526–35.
   PubMed Web of Science ®Google Scholar
• Malicki JJ, Johnson CA. The cilium: cellular antenna and central processing unit. Trends Cell Biol. 2017;27(2):126–140.
   PubMed Web of Science ®Google Scholar
• Christensen ST, Pedersen LB, Schneider L, et al. Sensory cilia and integration of signal transduction in human health and disease. Traffic (Copenhagen, Denmark). 2007;8(2):97–109.
   PubMed Web of Science ®Google Scholar
• Hildebrandt F, Otto E. Cilia and centrosomes: a unifying pathogenic concept for cystic kidney disease? Nat Rev Genet. 2005;6(12):928–940.
   PubMed Web of Science ®Google Scholar
• Wheway G, Parry DA, Johnson CA. The role of primary cilia in the development and disease of the retina. Organogenesis. 2014;10(1):69–85.
   PubMed Web of Science ®Google Scholar
• Gillingham AK, Munro S. The small G proteins of the Arf family and their regulators. Annu Rev Cell Dev Biol. 2007;23:579–611.
   PubMed Web of Science ®Google Scholar
• Bologna G, Yvon C, Duvaud S, et al. N-terminal myristoylation predictions by ensembles of neural networks. Proteomics. 2004;4(6):1626–1632.
   PubMed Web of Science ®Google Scholar
• Pasqualato S, Renault L, Cherfils J. Arf, Arl, Arp and Sar proteins: a family of GTP-binding proteins with a structural device for ‘front-back’ communication. EMBO Rep. 2002;3(11):1035–1041.
   PubMed Web of Science ®Google Scholar
• Tucker RW, Pardee AB, Fujiwara K. Centriole ciliation is related to quiescence and DNA synthesis in 3T3 cells. Cell. 1979;17(3):527–535.
   PubMed Web of Science ®Google Scholar
• De Robertis E. Electron microscope observations on the submicroscopic organization of the retinal rods. J Biophys Biochem Cytol. 1956;2(3):319–330.
   PubMedGoogle Scholar
• Allen RA. Isolated cilia in inner retinal neurons and in retinal pigment epithelium. J Ultrastruct Res. 1965;12(5):730–747.
   PubMedGoogle Scholar
• Yang J, Gao J, Adamian M, et al. The ciliary rootlet maintains long-term stability of sensory cilia. Mol Cell Biol. 2005;25(10):4129–4137.
   PubMed Web of Science ®Google Scholar
• Pan J, Wang Q, Snell WJ. Cilium-generated signaling and cilia-related disorders. Lab Invest. 2005;85(4):452–463.
   PubMed Web of Science ®Google Scholar
• Yoder BK. Role of primary cilia in the pathogenesis of polycystic kidney disease. J Am Soc Nephrol. 2007;18(5):1381–1388.
   PubMed Web of Science ®Google Scholar
• Leyssac PP. Changes in single nephron renin release are mediated by tubular fluid flow rate. Kidney Int. 1986;30(3):332–339.
   PubMed Web of Science ®Google Scholar
• Praetorius HA, Spring KR. Removal of the MDCK cell primary cilium abolishes flow sensing. J Membr Biol. 2003;191(1):69–76.
   PubMed Web of Science ®Google Scholar
• Yoder BK, Hou X, Guay-Woodford LM. The polycystic kidney disease proteins, polycystin-1, polycystin-2, polaris, and cystin, are co-localized in renal cilia. J Am Soc Nephrol. 2002;13(10):2508–2516.
   PubMed Web of Science ®Google Scholar
• D’Angelo A, Franco B. The dynamic cilium in human diseases. PathoGenetics. 2009;2(1):3.
   PubMedGoogle Scholar
• May-Simera HL, Kelley MW. Cilia, Wnt signaling, and the cytoskeleton. Cilia. 2012;1(1):7.
   PubMedGoogle Scholar
• Xin D, Christopher KJ, Zeng L, et al. IFT56 regulates vertebrate developmental patterning by maintaining IFTB complex integrity and ciliary microtubule architecture. Development. 2017;144(8):1544–1553.
   PubMed Web of Science ®Google Scholar
• Liem KF Jr., Ashe A, He M, et al. The IFT-A complex regulates Shh signaling through cilia structure and membrane protein trafficking. J Cell Biol. 2012;197(6):789–800.
   PubMed Web of Science ®Google Scholar
• Qin J, Lin Y, Norman RX, et al. Intraflagellar transport protein 122 antagonizes Sonic Hedgehog signaling and controls ciliary localization of pathway components. Proc Natl Acad Sci U S A. 2011;108(4):1456–1461.
   PubMed Web of Science ®Google Scholar
• Gerdes JM, Davis EE, Katsanis N. The vertebrate primary cilium in development, homeostasis, and disease. Cell. 2009;137(1):32–45.
   PubMed Web of Science ®Google Scholar
• Waters AM, Beales PL. Ciliopathies: an expanding disease spectrum. Pediatr Nephrol (Berlin, Germany). 2011;26(7):1039–1056.
   PubMed Web of Science ®Google Scholar
• Latour BL, Van De Weghe JC, Rusterholz TDS, et al. ARMC9 and TOGARAM1 define a Joubert syndrome-associated protein module that regulates axonemal post-translational modifications and cilium stability. bioRxiv. 2019;817213.
   Google Scholar
• Malicdan MC, Vilboux T, Stephen J, et al. Mutations in human homologue of chicken talpid3 gene (KIAA0586) cause a hybrid ciliopathy with overlapping features of Jeune and Joubert syndromes. J Med Genet. 2015;52(12):830–839.
   PubMed Web of Science ®Google Scholar
• Travaglini L, Brancati F, Silhavy J, et al. Phenotypic spectrum and prevalence of INPP5E mutations in Joubert syndrome and related disorders. Eur J Human Genet. 2013;21(10):1074–1078.
   PubMed Web of Science ®Google Scholar
• Joubert M, Eisenring JJ, Andermann F. Familial dysgenesis of the vermis: a syndrome of hyperventilation, abnormal eye movements and retardation. Neurology. 1968;18(3):302–303.
   PubMed Web of Science ®Google Scholar
• Doherty D. Joubert syndrome: insights into brain development, cilium biology, and complex disease. Semin Pediatr Neurol. 2009;16(3):143–154.
   PubMed Web of Science ®Google Scholar
• Valente EM, Brancati F, Dallapiccola B. Genotypes and phenotypes of Joubert syndrome and related disorders. Eur J Med Genet. 2008;51(1):1–23.
   PubMed Web of Science ®Google Scholar
• Srivastava S, Ramsbottom SA, Molinari E, et al. A human patient-derived cellular model of Joubert syndrome reveals ciliary defects which can be rescued with targeted therapies. Hum Mol Genet. 2017;26(23):4657–4667.
   PubMed Web of Science ®Google Scholar
• Humbert MC, Weihbrecht K, Searby CC, et al. ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting. Proc Natl Acad Sci U S A. 2012;109(48):19691–19696.
   PubMed Web of Science ®Google Scholar
• Fan Y, Esmail MA, Ansley SJ, et al. Mutations in a member of the Ras superfamily of small GTP-binding proteins causes Bardet-Biedl syndrome. Nat Genet. 2004;36(9):989–993.
   PubMed Web of Science ®Google Scholar
• Wiens CJ, Tong Y, Esmail MA, et al. Bardet-Biedl syndrome-associated small GTPase ARL6 (BBS3) functions at or near the ciliary gate and modulates Wnt signaling. J Biol Chem. 2010;285(21):16218–16230.
   PubMed Web of Science ®Google Scholar
• Roy K, Jerman S, Jozsef L, et al. Palmitoylation of the ciliary GTPase ARL13b is necessary for its stability and its role in cilia formation. J Biol Chem. 2017;292(43):17703–17717.
   PubMed Web of Science ®Google Scholar
• Avidor-Reiss T, Maer AM, Koundakjian E, et al. Decoding cilia function: defining specialized genes required for compartmentalized cilia biogenesis. Cell. 2004;117(4):527–539.
   PubMed Web of Science ®Google Scholar
• Blacque OE, Perens EA, Boroevich KA, et al. Functional genomics of the cilium, a sensory organelle. Curr Biol. 2005;15(10):935–941.
   PubMed Web of Science ®Google Scholar
• Zhou C, Cunningham L, Marcus AI, et al. Arl2 and Arl3 regulate different microtubule-dependent processes. Mol Biol Cell. 2006;17(5):2476–2487.
   PubMed Web of Science ®Google Scholar
• Zhang H, Constantine R, Vorobiev S, et al. UNC119 is required for G protein trafficking in sensory neurons. Nat Neurosci. 2011;14(7):874–880.
   PubMed Web of Science ®Google Scholar
• Hanzal-Bayer M, Renault L, Roversi P, et al. The complex of Arl2-GTP and PDE delta: from structure to function. Embo J. 2002;21(9):2095–2106.
   PubMed Web of Science ®Google Scholar
• Stephen LA, Ismail S. Shuttling and sorting lipid-modified cargo into the cilia. Biochem Soc Trans. 2016;44(5):1273–1280.
   PubMedGoogle Scholar
• Zhang H, Hanke-Gogokhia C, Jiang L, et al. Mistrafficking of prenylated proteins causes retinitis pigmentosa 2. Faseb J. 2015;29(3):932–942.
   PubMed Web of Science ®Google Scholar
• Ismail SA, Chen YX, Rusinova A, et al. Arl2-GTP and Arl3-GTP regulate a GDI-like transport system for farnesylated cargo. Nat Chem Biol. 2011;7(12):942–949.
   PubMed Web of Science ®Google Scholar
• Cavazza T, Vernos I. The RanGTP pathway: from nucleo-cytoplasmic transport to spindle assembly and beyond. Front Cell Dev Biol. 2015;3:82.
   PubMed Web of Science ®Google Scholar
• Yamada M, Mattaj IW, Yoneda Y. An ATP-dependent activity that releases RanGDP from NTF2. J Biol Chem. 2004;279(35):36228–36234.
   PubMed Web of Science ®Google Scholar
• Evans RJ, Schwarz N, Nagel-Wolfrum K, et al. The retinitis pigmentosa protein RP2 links pericentriolar vesicle transport between the Golgi and the primary cilium. Hum Mol Genet. 2010;19(7):1358–1367.
   PubMed Web of Science ®Google Scholar
• Stephan A, Vaughan S, Shaw MK, et al. An essential quality control mechanism at the eukaryotic basal body prior to intraflagellar transport. Traffic (Copenhagen, Denmark). 2007;8(10):1323–1330.
   PubMed Web of Science ®Google Scholar
• Hurd TW, Fan S, Margolis BL. Localization of retinitis pigmentosa 2 to cilia is regulated by Importin beta2. J Cell Sci. 2011;124(Pt 5):718–726.
   PubMed Web of Science ®Google Scholar
• Schrick JJ, Vogel P, Abuin A, et al. ADP-ribosylation factor-like 3 is involved in kidney and photoreceptor development. Am J Pathol. 2006;168(4):1288–1298.
   PubMed Web of Science ®Google Scholar
• Hanke-Gogokhia C, Wu Z, Gerstner CD, et al. Arf-like protein 3 (ARL3) regulates protein trafficking and ciliogenesis in mouse photoreceptors. J Biol Chem. 2016;291(13):7142–7155.
   PubMed Web of Science ®Google Scholar
• Schwarz N, Lane A, Jovanovic K, et al. Arl3 and RP2 regulate the trafficking of ciliary tip kinesins. Hum Mol Genet. 2017;26(13):2480–2492.
   PubMed Web of Science ®Google Scholar
• He M, Subramanian R, Bangs F, et al. The kinesin-4 protein KIF7 regulates mammalian Hedgehog signalling by organizing the cilium tip compartment. Nat Cell Biol. 2014;16(7):663–672.
   PubMed Web of Science ®Google Scholar
• Zhu Z, Tang NL, Xu L, et al. Genome-wide association study identifies new susceptibility loci for adolescent idiopathic scoliosis in Chinese girls. Nat Commun. 2015;6:8355.
   PubMed Web of Science ®Google Scholar
• Li C, Kim YK, Dorajoo R, et al. Genome-wide association study meta-analysis of long-term average blood pressure in East Asians. Circ Cardiovasc Genet. 2017;10(2):e001527.
   PubMedGoogle Scholar
• Yu H, Yan H, Li J, et al. Common variants on 2p16.1, 6p22.1 and 10q24.32 are associated with schizophrenia in Han Chinese population. Mol Psychiatry. 2017;22(7):954–960.
   PubMed Web of Science ®Google Scholar
• Darnell JE Jr. STATs and gene regulation. Science (New York, NY). 1997;277(5332):1630–1635.
   PubMed Web of Science ®Google Scholar
• Jove R. Preface: STAT signaling. Oncogene. 2000;19(21):2466–2467.
   PubMed Web of Science ®Google Scholar
• Levy DE, Darnell JE Jr. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3(9):651–662.
   PubMed Web of Science ®Google Scholar
• Bromberg J, Darnell JE Jr. The role of STATs in transcriptional control and their impact on cellular function. Oncogene. 2000;19(21):2468–2473.
   PubMed Web of Science ®Google Scholar
• Takeda K, Noguchi K, Shi W, et al. Targeted disruption of the mouse STAT3 gene leads to early embryonic lethality. Proc Natl Acad Sci U S A. 1997;94(8):3801–3804.
   PubMed Web of Science ®Google Scholar
• Akira S. Roles of STAT3 defined by tissue-specific gene targeting. Oncogene. 2000;19(21):2607–2611.
   PubMed Web of Science ®Google Scholar
• Okita K, Yamanaka S. Intracellular signaling pathways regulating pluripotency of embryonic stem cells. Curr Stem Cell Res Ther. 2006;1(1):103–111.
   PubMedGoogle Scholar
• Togi S, Muromoto R, Hirashima K, et al. A new STAT3-binding partner, ARL3, enhances the phosphorylation and nuclear accumulation of STAT3. J Biol Chem. 2016;291(21):11161–11171.
   PubMed Web of Science ®Google Scholar
• Breslow DK, Hoogendoorn S, Kopp AR, et al. A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies. Nat Genet. 2018;50(3):460–471.
   PubMed Web of Science ®Google Scholar
• Dustin ML. The immunological synapse. Cancer Immunol Res. 2014;2(11):1023–1033.
   PubMed Web of Science ®Google Scholar
• Griffiths GM, Tsun A, Stinchcombe JC. The immunological synapse: a focal point for endocytosis and exocytosis. J Cell Biol. 2010;189(3):399–406.
   PubMed Web of Science ®Google Scholar
• Stinchcombe JC, Griffiths GM. Communication, the centrosome and the immunological synapse. Philos Trans R Soc London, Ser B. 2014;369(1650):20130463.
   Web of Science ®Google Scholar
• Gawden-Bone CM, Frazer GL, Richard AC, et al. PIP5 kinases regulate membrane phosphoinositide and actin composition for targeted granule secretion by cytotoxic lymphocytes. Immunity. 2018;49(3):427–37.e4.
   PubMed Web of Science ®Google Scholar
• Dustin ML. T-cells play the classics with a different spin. Mol Biol Cell. 2014;25(11):1699–1703.
   PubMed Web of Science ®Google Scholar
• de la Roche M, Ritter AT, Angus KL, et al. Hedgehog signaling controls T cell killing at the immunological synapse. Science (New York, NY). 2013;342(6163):1247–1250.
   PubMed Web of Science ®Google Scholar
• Gorska MM, Liang Q, Karim Z, et al. Uncoordinated 119 protein controls trafficking of LCK via the RAB11 endosome and is critical for immunological synapse formation. J Iimmunol (Baltimore, Md: 1950). 2009;183(3):1675–1684.
   PubMed Web of Science ®Google Scholar
• Zlatkine P, Mehul B, Magee AI. Retargeting of cytosolic proteins to the plasma membrane by the LCK protein tyrosine kinase dual acylation motif. J Cell Sci. 1997;110(Pt 5):673–679.
   PubMedGoogle Scholar
• Gorska MM, Alam R. A mutation in the human Uncoordinated 119 gene impairs TCR signaling and is associated with CD4 lymphopenia. Blood. 2012;119(6):1399–1406.
   PubMed Web of Science ®Google Scholar
• Viau A, Bienaime F, Lukas K, et al. Cilia-localized LKB1 regulates chemokine signaling, macrophage recruitment, and tissue homeostasis in the kidney. Embo J. 2018;37(15):e98615.
   PubMed Web of Science ®Google Scholar