The primary cilium has an important role in signaling; defects in structure are associated with a variety of human diseases. Much of the most basic biology of this organelle is poorly understood, even basic mechanisms, such as control of growth and resorption. We show that the activity of the anaphase-promoting complex (APC), an E3 that regulates the onset of anaphase, destabilizes axonemal microtubules in the primary cilium. Furthermore, the metaphase APC co-activator, Cdc20, is specifically recruited to the basal body of primary cilia. Inhibition of APC-Cdc20 activity increases the ciliary length, while overexpression of Cdc20 suppresses cilium formation. APC-Cdc20 activity is required for the timely resorption of the cilium after serum stimulation. In addition, APC regulates the stability of axonemal microtubules through targeting Nek1, the ciliary kinase, for proteolysis. These data demonstrate a novel function of APC beyond cell cycle control and implicate critical role of ubiquitin-mediated proteolysis in ciliary disassembly.
The majority of cells in the human body have small hair-like structures that project from the cell surface. These structures, known as primary cilia, are involved in sensing light and touch, and they are also required for an organism to develop normally. Defects in cilia result in a wide range of human diseases that are collectively known as ciliopathies. These include polycystic kidney disease and Bardet–Biedl syndrome. Ciliary disorders can also affect almost every organ in the body leading to blindness, obesity, diabetes, and cancer.
Cilia are dynamic structures that are dis-assembled when cells start to divide and are then re-assembled when cells are quiescent. The anaphase promoting complex (APC) has a critical role during cell division and targets key proteins that need to be degraded at specific times during this process. APC is localized in the basal body, which is found at the bottom of cilia, and it works together with a number of proteins which assist its function.
Wang et al. now report that a complex formed by APC and its co-activator protein Cdc20 has two functions at the basal body: it is needed to maintain the optimal length of the cilia in quiescent cells and to shorten the cilia when cells exit from quiescent stage.
Wang et al. also investigated the role of Nek1, an enzyme that is localised in the basal body. It was found that reducing the level of Nek1 in quiescent cells resulted in the formation of defective cilia, suggesting that this enzyme controls the stability and integrity of cilia. Moreover, when cells undergo division, the APC-Cdc20 complex targets the Nek1 enzyme, causing it to be degraded and allowing the cilia to be disassembled. A detailed understanding of how cells maintain the length of cilia could lead to the development of new approaches for the treatment of human ciliopathies.