Control of ciliogenesis by FOR20, a novel centrosome and pericentriolar satellite protein

Abstract

SummaryCilia and flagella are evolutionary conserved organelles that generate fluid movement and locomotion, and play roles in chemosensation, mechanosensation and intracellular signalling. In complex organisms, cilia are highly diversified, which allows them to perform various functions; however, they retain a 9+0 or 9+2 microtubules structure connected to a basal body. Here, we describe FOR20 (FOPrelated protein of 20 kDa), a previously uncharacterized and highly conserved protein that is required for normal formation of a primary cilium. FOR20 is found in PCM1-enriched pericentriolar satellites and centrosomes. FOR20 contains a Lis1-homology domain that promotes self-interaction and is required for its satellite localization. Inhibition of FOR20 expression in RPE1 cells decreases the percentage of ciliated cells and the length of the cilium on ciliated cells. It also modifies satellite distribution, as judged by PCM1 staining, and displaces PCM1 from a detergent-insoluble to a detergent-soluble fraction. The subcellular distribution of satellites is dependent on both microtubule integrity and molecular motor activities. Our results suggest that FOR20 could be involved in regulating the interaction of PCM1 satellites with microtubules and motors. The role of FOR20 in primary cilium formation could therefore be linked to its function in regulating pericentriolar satellites. A role for FOR20 at the basal body itself is also discussed.

Mining the Giardia genome and proteome for conserved and unique basal body proteins

“…Examples are: Enolase (Johnstone et al, 1992), 14-3-3 protein (Pietromonaco et al, 1996), Bbc20 (Kilburn et al, 2007; Sedjai et al, 2010), BUG21/PACRG (Keller et al, 2005), and Ran (Chen et al, 1994). Instead, ours and others’ studies show that protein 14-3-3 (Lalle et al, 2006), enolase (Ringqvist et al, 2008), TCP-1 (Gene ID GL50803_11992) (Fig.…”

Regulation of centriolar satellite integrity and its physiology

“…In support of the significance of MSD1/SSX2IP localisation to centriolar satellites, depletion of PCM1, which disperses MSD1/SSX2IP from satellites, also results in microtubule-anchoring defects [24, 33]. Similar microtubule defects are also reported upon depletion of a series of satellite components that are required for proper localisation of PCM1 to the pericentriolar region; these include CEP90 [55, 56], FOR20 [64], HOOK3 [65] and Par6α [66]. Other proteins including CAP350, FOP, Ninein, ODF2/Cenexin1 and Trichoplein, among which FOP is a centriolar satellite component, are also involved in microtubule anchoring [33, 71–75].…”

“…These include CCDC11 [30], CCDC12 [26], CCDC13 [50], CCDC14 [23, 26], CCDC18 [26], CCDC66 [26], CEP63 [23, 51–53], CEP72 [54], CEP90 [55, 56], CEP126 [57], CEP131/AZI1 [26, 58–60], CEP290 (also called NPHP6) [38, 61–63], FOR20 [64], HAP1 and HTT [36, 65], KIAA0753 [23], Par6α [66] and SDCCAG8 [67]. However, in most of these cases, the underlying molecular mechanisms by which centriolar satellite integrity is disturbed have not yet been explored, and it remains to be determined whether alterations of centriolar satellite distributions are due to the failure of PCM1 oligomerisation, the compromised interaction of PCM1 with other components or perturbation of the association of PCM1 particles with microtubules (see below).…”

Discovery of Functional and Disease Pathways by Community Detection in Protein-Protein Interaction Networks

“…Despite this, FOPNL is well known to be associated with the biogenesis of cilia and BBS causative mutations upset cilial function. Furthermore, FOPNL interacts with PCM1 , a known BBS gene that is also suggested by community analysis 28 . For BBS, there is a lack of overlap between community predictions, which points to the fact that each method is dependent on different features and therefore provides unique insight.…”