TTC8
Description
The TTC8 (tetratricopeptide repeat domain 8) is a protein-coding gene located on chromosome 14.
TTC8, also known as Bardet–Biedl syndrome 8, is a protein encoded by the TTC8 gene in humans. It is associated with gamma-tubulin, BBS4, and PCM1 at the centrosome, playing a role in centriolar replication during ciliogenesis. TTC8 is found in the cilia of spermatids, retina, and bronchial epithelium cells. Mutations in the TTC8 gene are one of 14 known causes of Bardet–Biedl syndrome.
The BBSome complex, which TTC8 is a part of, acts as a coat complex that sorts specific membrane proteins to the primary cilia. This complex is essential for ciliogenesis but not for centriolar satellite function. TTC8 contributes to the complex's ciliogenic function by interacting with Rab8 GDP/GTP exchange factor, which localizes to the basal body and contacts the BBSome. Rab8(GTP) then enters the primary cilium and promotes the extension of the ciliary membrane. The BBSome associates with the ciliary membrane and binds to RAB3IP/Rabin8, the guanosyl exchange factor (GEF) for Rab8. This leads to Rab8-GTP localization to the cilium and promotes the docking and fusion of carrier vesicles to the base of the ciliary membrane. Along with LTZL1, the BBSome complex controls SMO ciliary trafficking and contributes to the regulation of the sonic hedgehog (SHH) pathway. TTC8 is crucial for the proper assembly and ciliary localization of the BBSome complex.
TTC8 is also known as BBS8, RP51.
