The distal appendage proteins recruit TTBK2

Stable Identifier
R-HSA-5626228
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

C2CD3 and the distal appendage protein CEP164 are required for the recruitment of the kinase Tau tubulin kinase 2 (TTBK2) to the centriole (Ye et al, 2014; Cajanek et al, 2014). TTBK2 recruitment promotes the release of CCP110, a negative regulator of ciliogenesis that caps the mother centriole (Goetz et al, 2012; Ye et al, 2014; Tsang et al, 2008; Spektor et al, 2007). CCP110 is initially recruited and/or stabilized at the mother centriole in a KIF24-dependent manner; KIF24, a kinesin-like protein, also restricts ciliogenesis through its microtubule depolymerizing activity (Kobayashi et al, 2011). In addition to promoting the release of CCP110, TTBK2 also plays a role in the recruitment of intraflagellar transport (IFT) proteins and in this way contributes to extension of the ciliary axoneme (Goetz et al, 2012; Ye et al, 2014). Mutations in TTBK2 disrupt ciliogenesis and are associated with the development of spinocerebellar ataxia (Houlden et al, 2007; Bouskila et al, 2011; reviewed in Jackson, 2012).

Literature References
PubMed ID Title Journal Year
18694559 CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease

Tsang, WY, Bossard, C, Khanna, H, Peršnen, J, Swaroop, A, Malhotra, V, Dynlacht, BD

Dev. Cell 2008
21620453 Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis

Kobayashi, T, Tsang, WY, Li, J, Lane, W, Dynlacht, BD

Cell 2011
24982133 Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole

CajŠnek, L, Nigg, EA

Proc. Natl. Acad. Sci. U.S.A. 2014
24469809 C2cd3 is critical for centriolar distal appendage assembly and ciliary vesicle docking in mammals

Ye, X, Zeng, H, Ning, G, Reiter, JF, Liu, A

Proc. Natl. Acad. Sci. U.S.A. 2014
21548880 TTBK2 kinase substrate specificity and the impact of spinocerebellar-ataxia-causing mutations on expression, activity, localization and development

Bouskila, M, Esoof, N, Gay, L, Fang, EH, Deak, M, Begley, MJ, Cantley, LC, Prescott, A, Storey, KG, Alessi, DR

Biochem. J. 2011
18037885 Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11

Houlden, H, Johnson, J, Gardner-Thorpe, C, Lashley, T, Hernandez, D, Worth, P, Singleton, AB, Hilton, DA, Holton, J, Revesz, T, Davis, MB, Giunti, P, Giunti, P, Wood, NW

Nat. Genet. 2007
23141531 TTBK2 kinase: linking primary cilia and cerebellar ataxias

Jackson, PK

Cell 2012
17719545 Cep97 and CP110 suppress a cilia assembly program

Spektor, A, Tsang, WY, Khoo, D, Dynlacht, BD

Cell 2007
23141541 The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis

Goetz, SC, Liem, KF, Anderson, KV

Cell 2012
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