Control of ciliogenesis by FOR20, a novel centrosome and pericentriolar satellite protein.
Cilia 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 (FOP-related 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.
Sedjaï
Fatima
F
Centre de Recherche en Cancérologie de Marseille, UMR 891 INSERM, F-13009 Marseille, France.
Acquaviva
Claire
C
Chevrier
Véronique
V
Chauvin
Jean-Paul
JP
Coppin
Emilie
E
Aouane
Aicha
A
Coulier
François
F
Tolun
Aslihan
A
Pierres
Michel
M
Birnbaum
Daniel
D
Rosnet
Olivier
O
D000818:Animals; D000911:Antibodies, Monoclonal / Q000302:isolation & purification / Q000378:metabolism; D001324:Autoantigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002461:Cell Line, Transformed; D018385:Centrosome / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002923:Cilia / Q000378:metabolism* / Q000473:pathology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D006801:Humans; D006825:Hybridomas; D008870:Microtubules / Q000378:metabolism / Q000473:pathology; D010802:Phylogeny; D015202:Protein Engineering; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D055213:Retinal Pigment Epithelium / Q000276:immunology / Q000378:metabolism* / Q000473:pathology
D000911:Antibodies, Monoclonal; D001324:Autoantigens; C553664:CEP20 protein, human; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C086074:PCM1 protein, human; D011506:Proteins; D034741:RNA, Small Interfering