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Basal bodies (BBs) are microtubule-based organelles that template and stabilize cilia at the cell surface. Centrins ubiquitously associate with BBs and function in BB assembly, maturation, and stability. Human POC5 (hPOC5) is a highly conserved centrin-binding protein that binds centrins through Sfi1p-like repeats and is required for building full-length, mature centrioles. Here, we use the BB-rich cytoskeleton ofTetrahymena thermophilato characterize Poc5 BB functions.TetrahymenaPoc5 (TtPoc5) uniquely incorporates into assembling BBs and is then removed from mature BBs prior to ciliogenesis. Complete genomic knockout ofTtPOC5leads to a significantly increased production of BBs yet a markedly reduced ciliary density, both of which are rescued by reintroduction of TtPoc5. A secondTetrahymena POC5-like gene,SFR1, is similarly implicated in modulating BB production. WhenTtPOC5andSFR1are co-deleted, cell viability is compromised, and levels of BB overproduction are exacerbated. Overproduced BBs display defective transition zone formation and a diminished capacity for ciliogenesis. This study uncovers a requirement for Poc5 in building mature BBs, providing a possible functional link betweenhPOC5mutations and impaired cilia.SUMMARY STATEMENTLoss ofTetrahymena thermophilaPoc5 reveals an important role for this centrin-binding protein in basal body maturation, which also impacts basal body production and ciliogenesis.

Cilia are microtubule-based appendages present on almost all vertebrate cell types where they mediate a myriad of cellular processes critical for development and homeostasis. In humans, impaired ciliary function is associated with an ever-expanding repertoire of phenotypically-overlapping yet highly variable genetic disorders, the ciliopathies. Extensive work to elucidate the structure, function, and composition of the cilium is offering hints that the “static” representation of the cilium is a gross oversimplification of a highly dynamic organelle whose functions are choreographed dynamically across cell types, developmental, and homeostatic contexts. Understanding this diversity will require discerning ciliary versus non-ciliary roles for classically-defined “ciliary” proteins; defining ciliary protein-protein interaction networks within and beyond the cilium; and resolving the spatiotemporal diversity of ciliary structure and function. Here, focusing on one evolutionarily conserved ciliary module, the intraflagellar transport system, we explore these ideas and propose potential future studies that will improve our knowledge gaps of the oversimplified cilium and, by extension, inform the reasons that underscore the striking range of clinical pathologies associated with ciliary dysfunction.