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:
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.
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.
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.
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.
Examples:
TC#	Name	Organismal Type	Example
8.A.170.1.1	The MKS1 (559 aas; 0 TMSs)-B9D2 (175 aas, possibly 1 N-terminal TMS)-B9D1 (204 aas, possibly 1 N-terminal TMS) diffusion barrier (transition zone (TZ)) complex. These proteins are components of the tectonic-like complex, a complex localized at the transition zone of primary cilia and acting as a barrier that prevents diffusion of transmembrane proteins between the cilia and plasma membranes. The complex is involved in centrosome migration to the apical cell surface during early ciliogenesis (Tammachote et al. 2009). It is required for ciliary structure and function, including a role in regulating length and appropriate number through modulating centrosome duplication. It may also be required for cell branching morphology. The Meckel Syndrome Protein, Meckelin, may be part of the complex (see TC#9.B.77.1.1). MKS1 interacts with Meckelin (TMEM67; MKS3; Dawe et al. 2007).