ARL13B-mediated ciliary trafficking of INPP5E

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Homo sapiens
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ARL13B is a ciliary-localized small GTPase with an atypical C-terminus containing a coiled coil domain and a proline rich domain (PRD) (Hori et al, 2008). Mutations in ARL13B are associated with the development of the ciliopathy Joubert's Syndrome (Cantagrel et al, 2008; Parisi et al, 2009). Studies in C. elegans and vertebrates suggest that ARL13B may play a role in stabilizing the interaction between the IFT A and B complexes and the kinesin-2 motors during anterograde traffic in the cilium (Cevik et al, 2010; Li et al, 2010; Cevik et al, 2013; reviewed in Li et al, 2012; Zhang et al, 2013). Recent work has shown an additional role for ARL13B in trafficking the inositol polyphosphate-5-phosphatase E (INPP5E) to the cilium through a network that also involves the phosphodiesterase PDE6D and the centriolar protein CEP164 (Humbert et al, 2012; Thomas et al, 2014; reviewed in Zhang et al, 2013). Mutations in INPP5E are also associated with the development of Joubert syndrome and other ciliopathies (Bielas et al, 2009; Jacoby et al, 2009; reviewed in Conduit et al, 2012).

Literature References
PubMed ID Title Journal Year
19876931 Clinical and molecular features of Joubert syndrome and related disorders

Parisi, MA

Am J Med Genet C Semin Med Genet 2009
18554500 Domain architecture of the atypical Arf-family GTPase Arl13b involved in cilia formation

Kikko, Y, Kobayashi, T, Katada, T, Kontani, K, Hori, Y

Biochem. Biophys. Res. Commun. 2008
22389062 The emerging role of Arf/Arl small GTPases in cilia and ciliopathies

Ling, K, Hu, J, Li, Y

J. Cell. Biochem. 2012
23150559 ARL13B, PDE6D, and CEP164 form a functional network for INPP5E ciliary targeting

Seo, S, Searby, CC, Li, Y, Pope, RM, Sheffield, VC, Humbert, MC, Weihbrecht, K

Proc. Natl. Acad. Sci. U.S.A. 2012
24339792 Active transport and diffusion barriers restrict Joubert Syndrome-associated ARL13B/ARL-13 to an Inv-like ciliary membrane subdomain

Mans, DA, Kida, K, Hetterschijt, L, Sanders, AA, Ueffing, M, van Reeuwijk, J, Katada, T, Man Wu, K, Clarke, L, Kaplan, OI, Cevik, S, Boldt, K, Letteboer, SJ, Roepman, R, van Beersum, SE, Kremer, H, Mullins, A, Blacque, OE, Van Wijk, E, Wdowicz, A, Horn, N, Kontani, K, Hori, Y

PLoS Genet. 2013
23548655 Molecular views of Arf-like small GTPases in cilia and ciliopathies

Ling, K, Hu, J, Zhang, Q

Exp. Cell Res. 2013
24166846 A homozygous PDE6D mutation in Joubert syndrome impairs targeting of farnesylated INPP5E protein to the primary cilium

Perrault, I, Romani, M, Saunier, S, Saada, J, Abhyankar, A, Filhol, E, Wright, KJ, Encha-Ravazi, F, Litzler, J, Lyonnet, S, Jackson, PK, Chassaing, N, Drummond, IA, Le Corre, S, Elkhartoufi, N, Attié-Bitach, T, Munnich, A, Baehr, W, Gleeson, JG, Valente, EM, Micalizzi, A, Thomas, S, Amiel, J, Kwong, M, Boddaert, N, Burglen, L, Vekemans, M, Casanova, JL

Hum. Mutat. 2014
18674751 Mutations in the cilia gene ARL13B lead to the classical form of Joubert syndrome

Marsh, SE, Attié-Bitach, T, Traver, D, Audollent, S, Swistun, D, Holden, KR, Ali, BR, Johnson, CA, Caspary, T, Brancati, F, Dobyns, WB, Glass, IA, Lindner, TH, Logan, CV, Al-Gazali, L, Hildebrandt, F, Bennett, C, Bielas, SL, Cantagrel, V, Otto, EA, Bertrand, JY, Silhavy, JL

Am. J. Hum. Genet. 2008
19668215 INPP5E mutations cause primary cilium signaling defects, ciliary instability and ciliopathies in human and mouse

Ayub, M, Compère, P, Kisseleva, MV, Hampshire, DJ, Cox, JJ, Gergely, F, Gayral, S, Riley, JH, Woods, CG, Jacoby, M, Pérez-Morga, D, Pernot, E, Schurmans, S, Schiffmann, SN, Blockmans, M

Nat. Genet. 2009
22828281 Inositol polyphosphate 5-phosphatases; new players in the regulation of cilia and ciliopathies

Conduit, SE, Mitchell, CA, Dyson, JM

FEBS Lett. 2012
20530210 The small GTPases ARL-13 and ARL-3 coordinate intraflagellar transport and ciliogenesis

Ling, K, Wei, Q, Hu, J, Li, Y, Zhang, Y

J. Cell Biol. 2010
19668216 Mutations in INPP5E, encoding inositol polyphosphate-5-phosphatase E, link phosphatidyl inositol signaling to the ciliopathies

Schurmans, S, Kayserili, H, Gayral, S, Brancati, F, Dallapiccola, B, Jacoby, M, Gleeson, JG, Swistun, D, Majerus, PW, Zaki, MS, Valente, EM, Silhavy, JL, Boltshauser, E, Kisseleva, MV, Scott, LC, Travaglini, L, Abdel-Aleem, A, Fazzi, E, Bayoumi, RA, Bielas, SL, Bertini, E, Al-Gazali, L, Field, SJ, Sztriha, L, Rosti, RO

Nat Genet 2009
20231383 Joubert syndrome Arl13b functions at ciliary membranes and stabilizes protein transport in Caenorhabditis elegans

Cottell, D, Kida, K, Foley-Fisher, C, Toivenon, T, Blacque, OE, Katada, T, Kontani, K, Kaplan, OI, Hori, Y, Cevik, S

J. Cell Biol. 2010
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