title: Characterization of CCDC28B reveals its role in ciliogenesis and provides insight to understand its modifier effect on Bardet-Biedl syndrome.
abstract: Bardet-Biedl syndrome (BBS) is a genetically heterogeneous disorder that is generally inherited in an autosomal recessive fashion. However, in some families, trans mutant alleles interact with the primary causal locus to modulate the penetrance and/or the expressivity of the phenotype. CCDC28B (MGC1203) was identified as a second site modifier of BBS encoding a protein of unknown function. Here we report the first functional characterization of this protein and show it affects ciliogenesis both in cultured cells and in vivo in zebrafish. Consistent with this biological role, our in silico analysis shows that the presence of CCDC28B homologous sequences is restricted to ciliated metazoa. Depletion of Ccdc28b in zebrafish results in defective ciliogenesis and consequently causes a number of phenotypes that are characteristic of BBS and other ciliopathy mutants including hydrocephalus, left-right axis determination defects and renal function impairment. Thus, this work reports CCDC28B as a novel protein involved in the process of ciliogenesis whilst providing functional insight into the cellular basis of its modifier effect in BBS patients.
authors.affiliation: Human Molecular Genetics Laboratory, Institut Pasteur de Montevideo, Mataojo 2020, 11400 Montevideo, Uruguay.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Cardenas-Rodriguez
authors.forename: Daniel P S
authors.initials: DP
authors.lastname: Osborn
authors.forename: Florencia
authors.initials: F
authors.lastname: Irigoín
authors.forename: Martín
authors.initials: M
authors.lastname: Graña
authors.forename: Héctor
authors.initials: H
authors.lastname: Romero
authors.forename: Philip L
authors.initials: PL
authors.lastname: Beales
authors.forename: Jose L
authors.initials: JL
authors.lastname: Badano
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology; D002460:Cell Line; D002923:Cilia / Q000235:genetics* / Q000502:physiology; D017124:Conserved Sequence; D003598:Cytoskeletal Proteins; D055785:Gene Knockdown Techniques; D006801:Humans; D017403:In Situ Hybridization; D008969:Molecular Sequence Data; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D013045:Species Specificity; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics* / Q000502:physiology; D029961:Zebrafish Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000235:genetics* / Q000502:physiology
chemical_list: C507668:CCDC28B protein, human; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; D029961:Zebrafish Proteins