Comparative Genomics Identifies a Flagellar and Basal Body Proteome that Includes the BBS5 Human Disease Gene

Abstract

Cilia and flagella are microtubule-based structures nucleated by modified centrioles termed basal bodies. These biochemically complex organelles have more than 250 and 150 polypeptides, respectively. To identify the proteins involved in ciliary and basal body biogenesis and function, we undertook a comparative genomics approach that subtracted the nonflagellated proteome of Arabidopsis from the shared proteome of the ciliated/flagellated organisms Chlamydomonas and human. We identified 688 genes that are present exclusively in organisms with flagella and basal bodies and validated these data through a series of in silico, in vitro, and in vivo studies. We then applied this resource to the study of human ciliation disorders and have identified BBS5, a novel gene for Bardet-Biedl syndrome. We show that this novel protein localizes to basal bodies in mouse and C. elegans, is under the regulatory control of daf-19, and is necessary for the generation of both cilia and flagella.

Specificity of Arl2/Arl3 signaling is mediated by a ternary Arl3‐effector‐GAP complex

“…Another tubulin-specific folding cofactor, CoC, is a GTPase-activating protein (GAP) for Arl3 [9]. Arl3 was found in screens for ciliary genes [10,11] and localizes to the connecting cilium of human photoreceptor cells, in line with observations that ciliary proteins are responsible for a range of diseases like polycystic kidney disease or retinitis pigmentosa [12,13].…”

“…HRG4, Arl3 and RP2 were all found in screens for ciliary genes [11]. They are important for the maintenance of photoreceptor cells, since knockouts of Arl3 or HRG4 cause strong retinal defects in mice and mutations of RP2 are causing retinitis pigmentosa [18,19,30].…”

Trypanosoma rhipicephalis sp. nov. (Protozoa: Kinetoplastida) isolated from Rhipicephalus microplus (Acari: Ixodidae) ticks in Rio de Janeiro, Brazil

“…The flagellum is considered a sophisticated structure in trypanosomes and problems regarding the expression of proteins responsible for the development of this organelle are related to the appearance of mutant forms without flagella. Bastin et al (1999) and Li et al (2004) studied axoneme proteins; comparing flagellated and nonflagellated parasites, they noticed that these proteins were present in flagellated forms and absent in non-flagellated forms. The reasons for this phenomenon are still unknown, but these facts point to the possibility that the appearance of these atypical forms may be the result of disruption during cell division, which leads to the inability to form and expend the flagellum.…”

Axonemal protofilament ribbons, DM10 domains, and the link to juvenile myoclonic epilepsy

“…In the kidney, ciliary defects result in polycystic kidney disease, which is one of the most common human genetic diseases [Pazour et al, 2002], and poor ciliary motility in lung causes severe respiratory problems [Whitelaw et al, 1981]. It is now clear that ciliary/basal body defects also underlie Bardet-Biedl syndrome, which involves a wide range of phenotypes including rod-cone dystrophy, polydactyly, obesity, mental retardation, and male hypogonadism [Li et al, 2004]. Recent studies in mammals [Ibanez-Tallon et al, 2004] and zebrafish [Kramer-Zucker et al, 2005] have revealed that hydrocephalus is associated with ciliary defects in the ependyma and spinal canal, and genetic analysis of Joubert syndrome has suggested a linkage between ciliary function and cerebellar development [Louie and Gleeson, 2005].…”