Tectonic Proteins Are Important Players in Non-Motile Ciliopathies.

Primary cilium is a ubiquitous, tiny organelle on the apex of the mammalian cells. Non-motile (primary) ciliopathies are diseases caused by the dysfunction of the primary cilium and they are characterized by diverse clinical and genetic heterogeneity. To date, nearly 200 genes have been shown to be associated with primary ciliopathies. Among them, tectonic genes are the important causative genes of ciliopathies. Tectonic proteins including TCTN1, TCTN2, and TCTN3 are important component proteins residing at the transition zone of cilia. Indeed, many ciliopathies have been reported to involve tectonics mutations, highlighting a pivotal role for tectonic proteins in ciliary functions. However, the specific functions of tectonic proteins remain largely enigmatic. Herein, we discuss the recent advances on the localization and structure of tectonic proteins and the functions of tectonic proteins. The increasing line of evidences demonstrates that tectonic proteins are required for ciliogenesis and regulate ciliary membrane composition. More importantly, Tectonic proteins play a vital role in the regulation of the Sonic Hedgehog (Shh) pathway; Tectonic deficient mice show the Shh pathway-related developmental defects. Tectonic proteins share similar functions including neural patterning and Gli3 processing but also each has a unique and indispensable role in the ciliogenesis and signaling pathways. At the same time, the mutations of tectonic genes are the causes of a serial of primary ciliopathies including Meckel-Gruber syndrome, Oral-facial-digital syndrome, and Joubert syndrome. Therefore, full understanding of functions of tectonic proteins will help to crack ciliopathies and improve life quality of patients by future gene therapy.