| 2004 |
BBS5 localizes to basal bodies in mouse and C. elegans, is under the regulatory control of transcription factor daf-19, and is necessary for the generation of both cilia and flagella, establishing it as a basal body/ciliary protein. |
Comparative genomics, in vivo localization studies in mouse and C. elegans, in vitro and in vivo functional validation |
Cell |
High |
15137946
|
| 2015 |
BBS5 (BBS-5 in C. elegans) directly interacts with BBS4 (BBS-4), and this interaction can be disrupted by a conserved mutation identified in human BBS4. BBS4 and BBS5 act redundantly within the BBSome to regulate ciliary removal (not ciliary entry or retrograde IFT transport) of sensory receptors for lysosomal degradation. Mammalian BBS4 and BBS5 also directly interact and coordinate the ciliary removal of polycystin 2. |
Co-immunoprecipitation, direct interaction assays, C. elegans co-depletion genetics, mammalian cell assays for polycystin 2 ciliary removal |
Scientific reports |
High |
26150102
|
| 2016 |
A retina-specific splice variant of BBS5 (BBS5L) is generated by cryptic splicing sites in Intron 7, producing a truncated protein (~26.5 kD) with a unique 24 amino acid C-terminus. This splice variant localizes to the connecting cilium of photoreceptors and interacts with arrestin1; binding of BBS5L to arrestin1 can be modulated by phosphorylation through protein kinase C. |
RT-PCR, immunoblot, immunofluorescence on retinal sections, immunoprecipitation pull-down, PKC phosphorylation assay |
PloS one |
Medium |
26867008
|
| 2014 |
A frameshift mutation in BBS5 (c.966dupT; p.Ala323CysfsX57) causes mislocalization of the mutant BBS5 protein, which fails to localize to the basal body. Mutant BBS5 mRNA cannot rescue the ciliopathy phenotypes of bbs5 morphant zebrafish (retinal layering defects, abnormal cardiac looping, cystic pronephric ducts with reduced cilia expression), demonstrating that correct BBS5 localization to the basal body is required for its function. |
Cell culture localization (mutant vs. wild-type BBS5), morpholino knockdown in zebrafish, mRNA rescue experiments |
Cilia |
Medium |
24559376
|
| 2020 |
BBS5 is required for cone photoreceptor protein trafficking: in Bbs5-/- mice, cone-specific proteins (M- and S-opsins, arrestin-4, CNGA3, GNAT2) are mislocalized, light-dependent arrestin-1 translocation is disrupted, and cone photoreceptor function is completely lost. Outer segment disk orientation is abnormal. Peripherin-2 localization was not affected, indicating cargo specificity. |
Bbs5 knockout mouse model, electroretinography, immunofluorescence, TUNEL staining, transmission electron microscopy |
Investigative ophthalmology & visual science |
High |
32776140
|
| 2021 |
Bbs5 loss-of-function in mice (congenital null via LacZ gene trap) causes obesity, craniofacial and skeletal defects, ventriculomegaly, infertility, and pituitary anomalies. Using a conditional allele, male fertility defects, ventriculomegaly, and pituitary abnormalities are only present when Bbs5 is disrupted prior to postnatal day 7 (developmental origin), whereas obesity arises independently of the age of Bbs5 loss, indicating distinct temporal requirements for BBS5 in different tissues. |
Conditional (Bbs5flox/flox) and constitutive (Bbs5-/-) knockout mouse models, timed Cre-mediated deletion, phenotypic analysis |
Human molecular genetics |
High |
33560420
|
| 2022 |
Bbs5 and nphp-4 show a genetically conserved interaction: nphp-4;bbs-5 double mutant C. elegans display synthetic phenotypes not seen in either single mutant. In mice, Nphp4;Bbs5 double mutants are not viable with fewer than expected triple-mutant offspring; postnatal conditional Bbs5 loss combined with Nphp4 mutation compromises survival. Cilia are still formed in double mutant mice, suggesting the exacerbated phenotype results from disrupted ciliary signaling rather than cilia loss. |
Mutagenesis screen in C. elegans, double-mutant genetic analysis in C. elegans, zebrafish, and mouse; conditional allele crossed to Nphp4 mutant |
Genetics |
High |
34850872
|
| 2016 |
The transcription factor PITX2 directly regulates BBS5 expression: dual luciferase assays confirmed that PITX2 targets the BBS5 promoter, and overexpression/knockdown of PITX2 in trabecular meshwork cells altered endogenous BBS5 expression. |
Dual luciferase reporter assay, PITX2 overexpression and knockdown in primary trabecular meshwork cell cultures, bioinformatics identification of PITX2 binding sites |
Gene |
Medium |
27520585
|
| 2023 |
Loss of BBS5 protein in patient-derived cells results in defects in ciliary structure (presence/absence and size of cilia) and ciliary function, specifically impaired Sonic Hedgehog (SHH) pathway signaling. |
Patient-derived cell analysis, ciliary structure measurement, Sonic Hedgehog pathway functional assay |
International journal of molecular sciences |
Medium |
37240074
|