Abstract
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.
Highlights
The primary cilium is a non-motile microtubule-based organelle, organized by the mother centriole
Immunostaining showed that anaphase-promoting complex (APC) subunit 2 (APC2) is localized to the basal body of the ciliated cells (Figure 1A and Figure 1—figure supplement 2A), consistent with the previous report that APC is localized to the basal body of motile cilia in the Xenopus epidermis (Ganner et al, 2009)
We found that the APC co-activator Cdc20 is localized to basal body of the primary cilium (Figure 1B), whereas Cdh1 did not show such localization (Figure1—figure supplement 3)
Summary
The primary cilium is a non-motile microtubule-based organelle, organized by the mother centriole (basal body). Though known for over a century, it received little interest until it was appreciated that it is highly enriched in receptors for various signaling pathways, including PDGF, calcium, receptor tyrosine kinases, Wnt, and Hh (Satir et al, 2010). The assembly of primary cilium is coupled to cell cycle exit and entry into quiescence. The primary cilium functions as a tumor suppressor organelle that regulates cell proliferation and differentiation (Pan et al, 2012). Dysfunctions of the primary cilium cause a set of human diseases, classified as ciliopathies, such as polycystic kidney diseases (Hildebrandt et al, 2011). Cancers are associated with the loss of cilia, due to misregulated cell proliferation through ciliary signaling (Plotnikova et al, 2008)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
