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8.A.170.  The B9-Domain Protein Complex Diffusion Barrier for Ciliary Membrane Proteins (CB9DB) Family

Cilia in eukaryotes are plasma membrane protrusions that act as cellular antennae and propellers. To achieve their sensory and motile functions, cilia maintain protein and lipid compositions that are distinct from those of the cell body. The transition zone (TZ) is a specialized region located at the ciliary base, which functions as a barrier separating the interior and exterior of cilia. The TZ consissts of a number of transmembrane and soluble proteins. Meckel syndrome (MKS)1, B9 domain (B9D)1/MKS9, and B9D2/MKS10 are soluble TZ proteins that are encoded by causative genes of MKS and have a B9D in common. Okazaki et al. 2020 demonstrated the interaction mode of these B9D proteins to be MKS1-B9D2-B9D1 and demonstrated their interdependent localization to the TZ. Phenotypic analyses of MKS1-knockout (KO) and B9D2-KO cells show that the B9D proteins are involved in, although not essential for, normal cilia biogenesis. Rescue experiments of these KO cells showed that formation of the B9D protein complex is crucial for creating a diffusion barrier for ciliary membrane proteins. MKS1 interacts with meckelin (TMEM67; MKS3) which in turn interacts with Nesprin-2 (Q8WXH0; Dawe et al. 2009).

References associated with 8.A.170 family:

Dawe, H.R., M. Adams, G. Wheway, K. Szymanska, C.V. Logan, A.A. Noegel, K. Gull, and C.A. Johnson. (2009). Nesprin-2 interacts with meckelin and mediates ciliogenesis via remodelling of the actin cytoskeleton. J Cell Sci 122: 2716-2726. 19596800
Dawe, H.R., U.M. Smith, A.R. Cullinane, D. Gerrelli, P. Cox, J.L. Badano, S. Blair-Reid, N. Sriram, N. Katsanis, T. Attie-Bitach, S.C. Afford, A.J. Copp, D.A. Kelly, K. Gull, and C.A. Johnson. (2007). The Meckel-Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation. Hum Mol Genet 16: 173-186. 17185389
Okazaki, M., T. Kobayashi, S. Chiba, R. Takei, L. Liang, K. Nakayama, and Y. Katoh. (2020). Formation of the B9-domain protein complex MKS1-B9D2-B9D1 is essential as a diffusion barrier for ciliary membrane proteins. Mol. Biol. Cell 31: 2259-2268. 32726168
Tammachote, R., C.J. Hommerding, R.M. Sinders, C.A. Miller, P.G. Czarnecki, A.C. Leightner, J.L. Salisbury, C.J. Ward, V.E. Torres, V.H. Gattone, 2nd, and P.C. Harris. (2009). Ciliary and centrosomal defects associated with mutation and depletion of the Meckel syndrome genes MKS1 and MKS3. Hum Mol Genet 18: 3311-3323. 19515853