Centrin2 regulates CP110 removal in primary cilium formation.
Bottom Line: We disrupted CETN2 in human retinal pigmented epithelial cells, and despite having intact centrioles, they were unable to make cilia upon serum starvation, showing abnormal localization of distal appendage proteins and failing to remove the ciliation inhibitor CP110.Knockdown of CP110 rescued ciliation in CETN2-deficient cells.Thus, centrin2 regulates primary ciliogenesis through controlling CP110 levels.
Affiliation: Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, Ireland.Show MeSH
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Mentions: Exit from the cell cycle into quiescence has long been established as potentiating ciliogenesis (Dingemans, 1969; Seeley and Nachury, 2010). We tested whether the chicken DT40 lymphocyte cell line could be induced to undergo primary ciliation. Serum starvation of chicken B-lymphocyte DT40 cells led to cell cycle delay (Fig. 1, a and b) and a reproducible induction of primary cilia (Fig. 1, c and d). The ability to induce cilia in DT40 cells allowed us to explore the roles of centrin in ciliogenesis. Examining a series of genetically defined centrin knockout lines (Dantas et al., 2011), we found that centrin2 deficiency led to a significant decline in ciliation capacity that was as extensive as the decline seen in cells that lacked all three chicken centrin isoforms. Although the expression of centrin3 and centrin4 could partially rescue the absence of all chicken centrins in ciliogenesis, only the expression of centrin2 led to a complete rescue of the ability of DT40 cells to make primary cilia after serum starvation (Fig. 1 e), demonstrating that centrin2 is required for ciliation in lymphocytes. Centrin2 depletion in zebrafish gave rise to several ciliopathy phenotypes (Delaval et al., 2011) and a mouse knockout also revealed marked ciliopathy that was restricted to specific tissues (Ying et al., 2014). It was concluded that the murine phenotype in affected tissues was caused by problems in ciliary trafficking, with normal ciliogenesis initiation and axoneme formation (Ying et al., 2014). Given the partial rescue of ciliation that we see with centrin3 and centrin4 in the chicken model, it is possible that the interplay between the individual members of the centrin family determines the precise roles of an individual centrin in a given tissue.
Affiliation: Centre for Chromosome Biology, School of Natural Sciences, National University of Ireland, Galway, Galway, Ireland.