A "so cilia" network: cilia proteins start "social" networking

Abstract

Cilia are unique cellular organelles found in nearly all cell types. In recent years, the importance of these organelles has been highlighted by the discovery that mutations in genes encoding proteins related to cilia biogenesis and function cause a class of complex syndromes termed ciliopathies. Emerging evidence suggests interactions among the various ciliopathy-associated proteins, but the precise mechanisms by which these interactions generate functional networks have remained elusive. In this issue of the JCI, Rachel and colleagues have now clearly linked two ciliopathy-associated proteins (CEP290 and MKKS). Surprisingly, the effects of a hypomorphic disease-causing Cep290 allele were rescued by loss of MKKS function, suggesting that it might be possible to treat some ciliopathies by fine-tuning interactions within the expanding ciliary network.

Figure 1. The cilia.

(A) Primary cilia are nonmotile, as their axonemal microtubules have 9 microtubule pairs (9 + 0). (B) Motile cilia have an additional pair of central microtubules (9 + 2).

Figure 2. Scheme of the photoreceptor cell.

The connecting cilium is a specialized organelle that regulates trafficking into and out of the outer segment of the photoreceptor cell. CEP290 is found at the transition zone adjacent to the basal body where MKKS is localized. Given their localization at this strategic transport zone between the inner and outer segments, these two proteins act together to regulate ciliogenesis, possibly by controlling the trafficking of various cargos and proteins, including BBS and IFT proteins. RPE, retinal pigment epithelium.