Reactome | The distal appendage proteins recruit TTBK2

The distal appendage proteins recruit TTBK2

Stable Identifier

R-HSA-5626228

Type

Reaction

Species

Homo sapiens

Compartment

cytosol

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The distal appendage proteins recruit TTBK2

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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
21620453	Centriolar kinesin Kif24 interacts with CP110 to remodel microtubules and regulate ciliogenesis Dynlacht, BD, Li, J, Lane, W, Kobayashi, T, Tsang, WY	Cell	2011
18694559	CP110 suppresses primary cilia formation through its interaction with CEP290, a protein deficient in human ciliary disease Bossard, C, Dynlacht, BD, Khanna, H, Swaroop, A, Malhotra, V, Peränen, J, Tsang, WY	Dev. Cell	2008
24982133	Cep164 triggers ciliogenesis by recruiting Tau tubulin kinase 2 to the mother centriole Cajánek, 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 Zeng, H, Ning, G, Liu, A, Reiter, JF, Ye, X	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 Prescott, A, Bouskila, M, Cantley, LC, Gay, L, Alessi, DR, Storey, KG, Begley, MJ, Esoof, N, Deak, M, Fang, EH	Biochem. J.	2011
18037885	Mutations in TTBK2, encoding a kinase implicated in tau phosphorylation, segregate with spinocerebellar ataxia type 11 Davis, MB, Singleton, AB, Lashley, T, Revesz, T, Holton, J, Houlden, H, Hilton, DA, Worth, P, Johnson, J, Giunti, P, Gardner-Thorpe, C, Wood, NW, Hernandez, D, Giunti, P	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 Dynlacht, BD, Spektor, A, Khoo, D, Tsang, WY	Cell	2007
23141541	The spinocerebellar ataxia-associated gene Tau tubulin kinase 2 controls the initiation of ciliogenesis Liem, KF, Anderson, KV, Goetz, SC	Cell	2012