Elucidating the Role of TTBK2 in Cilia Stability

Abstract

Cilia are hair-like structures found on a number of cells serving a variety of different functions. The common denominator between cilia is that they are made up of a microtubule-based projection called the axoneme and nucleated by a modified mother centriole termed the basal body. While there has been an extensive amount of work interrogating ciliogenesis, the requirements for cilia maintenance has less been appreciated. Recent work is also starting to reveal that the cilia biogenesis pathways for these different cilia are different, suggesting that the requirements for their maintenance may also be different. TTBK2 is a key regulator of primary cilia assembly. In the following study, we identify novel pathways that regulate and are regulated by TTBK2 using BioID. Using tamoxifen-inducible Cre-recombinase cell and mouse systems, we are able to allow these systems to build cilia, deplete TTBK2 levels after cilia formation by tamoxifen induction, assess changes to different types of cilia over time, and validate some of the protein interactions we identified by BioID.