| 2010 |
Mouse Intu null mutants exhibit severe ciliogenesis defects (loss of primary cilia in embryos and cultured fibroblasts), disrupted Gli3 proteolytic processing, and downregulated Hh target genes Gli1 and Ptch1, establishing Intu as an essential regulator of ciliogenesis and Hedgehog signal transduction. A cytoplasmic GFP-Intu fusion protein efficiently rescues ciliogenic defects in Intu mutant cells. |
Gene-targeted null mutation in mice, immunofluorescence for cilia, qRT-PCR and Western blot for Hh pathway components, rescue with GFP-Intu in cultured fibroblasts |
Developmental biology |
High |
20067783
|
| 2009 |
Fuz (a PCP effector functionally linked to Intu in the same pathway) is essential for trafficking of cargo to basal bodies and to apical cilia tips, and for exocytosis in secretory cells; a Rab-related small GTPase was identified as a Fuz interaction partner also required for ciliogenesis and secretion, placing the PCP effector module at the interface of vesicle trafficking and ciliogenesis. |
Fuz mutant mouse analysis, in vivo mucociliary epithelium imaging, bioinformatics, co-immunoprecipitation/interaction with Rab GTPase |
Nature cell biology |
Medium |
19767740
|
| 2011 |
The ciliogenesis-dependent neural tube patterning functions of Intu and Fuz are non-redundant; genetic removal of both genes does not produce a convergent-extension phenotype, and neither gene shows genetic interaction with the core PCP regulator Vangl2 in convergent extension. Intu and Fuz double mutants show more severe patterning defects without redundancy, positioning these effectors downstream of core PCP but upstream of cilia-dependent Hh patterning. |
Intu;Fuz double mutant mouse analysis, genetic epistasis with Vangl2 hypomorph, histological and molecular patterning assays |
Developmental dynamics |
Medium |
21761479
|
| 2012 |
Tissue-specific disruption of Intu in embryonic epidermis causes near-complete loss of primary cilia in epidermal and follicular keratinocytes, suppresses Hedgehog signaling, and arrests hair follicle morphogenesis due to failure of follicular keratinocyte differentiation, without affecting epidermal stratification, barrier function, or planar cell polarity—demonstrating a cell-fate-specific, cilia-dependent role for Intu in skin. |
Conditional knockout (Cre-lox) in mouse epidermis, immunofluorescence for cilia markers, Hh pathway reporter analysis, histological differentiation assays |
Cell death and differentiation |
High |
22935613
|
| 2015 |
A hypomorphic Intu allele carrying a conserved hydrophobic-to-asparagine substitution (I813N) near the C-terminus causes moderate cilia loss, skeletal defects (rib defects, delayed endochondral ossification, polydactyly), and reduced Hh signaling, while neural tube patterning and PCP appear normal. The Intu(I813N) protein exhibits compromised ability to restore ciliogenesis in Intu null cells, functionally linking this residue to ciliogenic activity. |
Gene-targeted hypomorphic knock-in mouse (I813N), cilia quantification, skeletal staining, qRT-PCR for Hh targets, rescue assay in Intu null cultured cells |
Developmental dynamics |
High |
25774014
|
| 2017 |
INTU is essential for IFT-A (intraflagellar transport A) complex assembly during ciliogenesis. In an oncogenic SmoM2-driven basal cell carcinoma model, Intu disruption prevents BCC formation by suppressing primary cilia formation and Hh signaling. In mouse embryonic fibroblasts, depleting Intu blocks Smo agonist-induced Hh pathway activation, but expression of constitutively active Gli2ΔN restores Hh signaling in Intu-deficient cells, genetically placing INTU upstream of Gli2 activation and downstream of Smo. |
Conditional knockout in SmoM2 BCC mouse model, shRNA knockdown, cilia quantification, IFT-A complex assembly assays, epistasis with Gli2ΔN in MEFs |
Oncogene |
High |
28459465
|
| 2017 |
RSG1 (a small GTPase) localizes to the mother centriole in a process that depends on INTU (the CPLANE protein Inturned), tau tubulin kinase 2 (TTBK2), and RSG1's own GTPase activity. Loss of RSG1 impairs axonemal microtubule elongation after ciliary vesicle docking, placing RSG1 as a downstream effector of INTU at a final maturation step of cilia initiation. |
Rsg1 mouse knockout, immunofluorescence for RSG1 centriolar localization, genetic epistasis with Intu and TTBK2, cilia ultrastructure analysis, Hh pathway readouts |
The Journal of cell biology |
High |
29038301
|
| 2018 |
INTU physically interacts with STAT1; they co-localize at the centriole/basal body. INTU promotes proteasomal degradation of STAT1. In vitro, INTU expression preserves cilia length and cell viability after stress, effects antagonized by STAT1 overexpression. Kidney-proximal-tubule-specific ablation of Intu aggravates renal ischemia-reperfusion injury and impairs post-injury ciliogenesis. |
Co-immunoprecipitation, co-localization by immunofluorescence, conditional KO mouse (proximal tubule-specific), proteasome inhibitor assay, cell viability assays |
Nature communications |
High |
29581513
|
| 2020 |
Computational evolutionary analysis identifies INTU and FUZ as a heterodimeric complex homologous to HerMon (Hermansky-Pudlak syndrome and MON1-CCZ1) complexes, each containing triplicated Longin domains. Based on homology to known Rab effectors/GEFs, the INTU/FUZ complex is predicted to act as a GEF for Rab GTPases involved in ciliogenesis. |
Coevolution-based contact prediction, sequence conservation analysis (computational/bioinformatic) |
Bioinformatics |
Low |
31562761
|
| 2022 |
CPLANE complex (composed of INTU, FUZ, and WDPCP, which interact with JBTS17 and RSG1) is required for IFT-A particle assembly and intraflagellar transport; defects in CPLANE components disrupt PCP and Hh signaling, leading to ciliopathies including orofacial-digital syndrome and Bardet-Biedl syndrome. |
Synthesis/review of genetic and functional studies; functional studies cited include IFT-A assembly assays and mouse genetic models |
Biomolecules |
Medium |
35740972
|
| 2022 |
Conditional knockout of Intu in kidney tubules delays kidney repair and ameliorates renal fibrosis after ischemia-reperfusion injury. Intu KO kidneys show less senescence but higher cell proliferation and apoptosis during repair. In vitro, Intu knockdown suppresses scratch wound healing in renal tubular cells, accompanied by abnormal centrosome orientation, establishing a role for Intu in centrosome-directed tubular cell migration/repair. |
Conditional KO mouse (kidney tubule-specific), histological and biochemical analysis of fibrosis and senescence, scratch wound healing assay with centrosome orientation imaging |
The American journal of pathology |
Medium |
36586478
|
| 2024 |
Loss of Intu severely disrupts growth and branching morphogenesis of mouse embryonic lungs, associated with greatly reduced primary cilia in epithelial and mesenchymal cells and reduced Hh target gene expression (Gli1, Ptch1). Smoothened agonist increases Hh target gene expression and tubulogenesis in wild-type but not Intu mutant lung explants. Removing both Gli2 and Intu completely abolishes lung branching morphogenesis, genetically placing Intu upstream of Gli2-dependent Hh signaling in the lung. |
Intu null mouse KO, lung explant culture with Smo agonist, Gli2;Intu double mutant epistasis, qRT-PCR/immunofluorescence, transcriptomics |
Developmental biology |
High |
39029571
|
| 2025 |
The predicted PDZ domain unique to Inturned among TLD proteins does not interact with membranes or with Vangl2. Crystal structure of the Intu-PDZ domain reveals a unique PDZ-like fold lacking a canonical interaction site for PDZ-binding motifs. Vangl2 instead shows a phosphorylation-dependent interaction with a PDZ domain of the apical-basal polarity protein Scribble. |
Crystal structure determination of Intu-PDZ domain, biochemical binding assays (pulldown/binding experiments with membranes and Vangl2), structural analysis |
FEBS letters |
High |
41797376
|
| 2025 |
Functional studies in patient-derived cells with compound heterozygous INTU variants demonstrate altered ciliogenesis and/or cilia signaling, confirming that pathogenic INTU variants cause human disease through disruption of CPLANE-dependent ciliogenesis. |
Patient-derived cell ciliogenesis assays (compound heterozygous INTU variants), trio whole-exome sequencing |
HGG advances |
Medium |
40968537
|