Ask about this productRelated genes to: RABL4 antibody
- Gene:
- IFT27 NIH gene
- Name:
- intraflagellar transport 27
- Previous symbol:
- RABL4
- Synonyms:
- RAYL, BBS19
- Chromosome:
- 22q12.3
- Locus Type:
- gene with protein product
- Date approved:
- 2002-05-09
- Date modifiied:
- 2016-10-05
Related products to: RABL4 antibody
Related articles to: RABL4 antibody
- Specific G-protein-coupled receptors (GPCRs) exist on the ciliary membrane. Hedgehog signaling activation triggers the import of Smoothened into and export of GPR161 from cilia. The BBSome, which comprises eight Bardet-Biedl syndrome (BBS) proteins, mediates GPCR export, together with the intraflagellar transport (IFT) machinery, containing the IFT-A and IFT-B complexes. The absence of any BBSome subunit or IFT27 (also known as BBS19) (an IFT-B subunit) impairs ciliary GPCR export, including that of GPR161. Plasma membrane GPCRs undergo phosphorylation by GPCR kinases (GRKs) and subsequent binding of β-arrestins [β-arrestin1 (ARRB1) and β-arrestin2 (ARRB2)], which is crucial for clathrin-mediated endocytosis. We here confirmed that GPR161 and β-arrestin are accumulated within cilia in the absence of IFT27 or the BBSome, and that ARRB1 and ARRB2 double-knockout impairs GPR161 export. Notably, we found that activation-mimetic β-arrestin mutants can interact with both the BBSome and ciliary GPCRs, and cause constitutive export of GPR161. Moreover, we demonstrated that GRK2 plays a crucial role in GPR161 export. We here propose that phosphorylated GPR161 recruits β-arrestins, converting them into their activated conformation. Activated β-arrestins then interact with the BBSome, which connects them to the IFT machinery to facilitate GPR161 export. - Source: PubMed
Publication date: 2025/06/20
Fujii TaijuMurai NorihitoAso ShinyaTakatsu HiroyukiShin Hye-WonKatoh YoheiNakayama Kazuhisa - Ciliopathies are rare genetic diseases marked by considerable phenotypic heterogeneity and overlap. Among the key mechanisms of cilium biology, its compartmentalization is achieved through gating complexes and active transport such as intraflagellar transport (IFT). Among the IFT components, IFT27 plays a role in BBSome-mediated transport of ciliary membrane proteins required for ciliary signaling. While this gene was first linked to Bardet-Biedl syndrome, we next expanded its phenotypic spectrum to a fetal lethal ciliopathy. Here, we identified a second fetal case with short ribs, polydactyly, hypodysplastic kidneys, imperforate anus, and situs inversus. Genome sequencing identified novel biallelic variants in IFT27. Functional analysis of tissues from both fetal cases revealed that all the identified variants lead to mRNA decay. Immunohistochemistry on fetal kidney sections showed that those variants are associated with altered ciliogenesis. Overall, we showed that complete loss of IFT27 function leads to a severe phenotypic spectrum overlapping with short ribs polydactyly and Pallister-Hall syndromes. In addition, our results argue for a role of IFT27 in ciliogenesis in humans. - Source: PubMed
Publication date: 2025/02/15
Haïm DavidRoux NathalieBoutaud LucileVerlin LaureQuélin ChloéMoncler CandiceBourgon NicolasAchaiia AmaleRoth PhilippeMarijon PierreVanlieferinghen SarahThomas SophieAttié-Bitach Tania - Dry eye disease is the most common ocular surface disease globally, requiring a more effective treatment. We observed that a high-fat diet induced macrophage polarization to M1 and further induced inflammation in the meibomian and lacrimal glands. A four-week treatment with melatonin (MLT) eye drops can regulate macrophage polarization and alleviate dry eye signs. To investigate the therapeutic effects and mechanisms of action of MLT on high-fat-diet-induced dry eye disease in mice, RAW 264.7 cells pretreated with LPS and/or MLT underwent digital RNA with the perturbation of genes sequencing (DRUG-seq). Results showed that IFT27 was up-regulated, and MAPK pathways were suppressed after MLT pre-treatment. ERK/JNK phosphorylation was reduced in meibomian glands of MLT-treated dry eye mice and increased in IFT27 knockdown RAW 264.7 cells. In summary, MLT regulated macrophage polarization via IFT27 and reduced ERK/JNK phosphorylation. These results support that MLT is a promising medication for dry eye disease. - Source: PubMed
Publication date: 2024/06/24
Cai YuyingZhang XinYang ChuanxiJiang YapingChen Yihui - Approximately a quarter of Retinitis Pigmentosa (RP) is caused by mutations in transport-related genes in cilia. IFT27 (Intraflagellar Transport 27), a core component of the ciliary intraflagellar transport (IFT) system, has been implicated as a significant pathogenic gene in RP. The pathogenic mechanisms and subsequent pathology related to IFT27 mutations in RP are largely obscure. Here, we utilized TALEN technology to create an ift27 knockout (ift27) zebrafish model. Electroretinography (ERG) detection showed impaired vision in this model. Histopathological examinations disclosed that ift27 mutations cause progressive degeneration of photoreceptors in zebrafish, and this degeneration was late-onset. Immunofluorescence labeling of outer segments showed that rods degenerated before cones, aligning with the conventional characterization of RP. In cultured human retinal pigment epithelial cells, we found that IFT27 was involved in maintaining ciliary morphology. Furthermore, decreased IFT27 expression resulted in the inhibition of the Hedgehog (Hh) signaling pathway, including decreased expression of key factors in the Hh pathway and abnormal localization of the ciliary mediator Gli2. In summary, we generated an ift27 zebrafish line with retinal degeneration which mimicked the symptoms of RP patients, highlighting IFT27's integral role in the long-term maintenance of cilia via the Hh signaling pathway. This work may furnish new insights into the treatment or delay of RP caused by IFT27 mutations. - Source: PubMed
Publication date: 2024/02/02
Han ShanshanHu YueJia DannaLv YuexiaLiu MugenWang DechengChao JinXia XuanWang QiongLiu PeiCai YuRen Xiang - Owing to their crucial roles in development and homeostasis, defects in cilia cause ciliopathies with diverse clinical manifestations. The intraflagellar transport (IFT) machinery, containing the IFT-A and IFT-B complexes, mediates not only the intraciliary bidirectional trafficking but also import and export of ciliary proteins together with the kinesin-2 and dynein-2 motor complexes. The BBSome, containing eight subunits encoded by causative genes of Bardet-Biedl syndrome (BBS), connects the IFT machinery to ciliary membrane proteins to mediate their export from cilia. Although mutations in subunits of the IFT-A and dynein-2 complexes cause skeletal ciliopathies, mutations in some IFT-B subunits are also known to cause skeletal ciliopathies. We here show that compound heterozygous variations of an IFT-B subunit, IFT81, found in a patient with skeletal ciliopathy cause defects in its interactions with other IFT-B subunits, and in ciliogenesis and ciliary protein trafficking when one of the two variants was expressed in IFT81-knockout (KO) cells. Notably, we found that IFT81-KO cells expressing IFT81(Δ490-519), which lacks the binding site for the IFT25-IFT27 dimer, causes ciliary defects reminiscent of those found in BBS cells and those in IFT74-KO cells expressing a BBS variant of IFT74, which forms a heterodimer with IFT81. In addition, IFT81-KO cells expressing IFT81(Δ490-519) in combination with the other variant, IFT81 (L645*), which mimics the cellular conditions of the above skeletal ciliopathy patient, demonstrated essentially the same phenotype as those expressing only IFT81(Δ490-519). Thus, our data indicate that BBS-like defects can be caused by skeletal ciliopathy variants of IFT81. - Source: PubMed
Tasaki KoshiZhou ZhuangIshida YamatoKatoh YoheiNakayama Kazuhisa