Tectonics form a transition zone complex of ciliopathy proteins that regulate ciliary composition

Primary cilia are projections found on many human cells. These cilia do not move, but function as cellular antennae to receive and interpret signals. For example, olfactory cilia sense signals from the environment, such as odorants. Other cilia sense cues from other cells, such as Hedgehog proteins, to coordinate tissue patterning and growth. We have identified mechanisms of ciliary signaling, cilium formation, and the regulation of ciliary composition. Defects in ciliary signaling cause some forms of birth defects, cancer, polycystic kidney disease, and other disorders collectively called ciliopathies. Investigating ciliopathies is illuminating how disturbing the function of a single organelle can give rise to diverse human diseases. We have found that two ciliary proteins of the Tectonic family, Tctn1 and Tctn2, form part of the transition zone, a region at the base of the cilium. Tctn1 is an extracytosolic glycoprotein that interacts with transmembrane components of the transition zone such as Tmem67 to connect to a cytosolic transition zone complex comprised of most known Joubert‐ and Meckel‐associated proteins. Loss of components of the Tectonic transition zone complex in mice compromise ciliogenesis in some tissues, and deregulate ciliary protein composition in others. We hypothesize that transition zone defects disrupt intercellular signaling, causing the multiorgan disease observed in ciliopathies, including polycystic kidney disease and birth defects such as polydactyly.