ArticleGenes & development2011
An ARL3-UNC119-RP2 GTPase cycle targets myristoylated NPHP3 to the primary cilium.
Article in Genes & development, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 146 papers.
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Who cites it
146 citing papers in PubMed.
- De Novo Occurrence of a Variant in ARL3 and Apparent Autosomal Dominant Transmission of Retinitis Pigmentosa.PloS one · 2016Trial
- CFAP100 forms phase-separated condensates required for ciliary transition zone assembly.Nature communications · 2026Article
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- Disruption of the human cystin-1 myristoyl-electrostatic switch causes polycystic kidney disease that phenocopies autosomal recessive polycystic kidney disease.Kidney international · 2026Article
- Mechanisms controlling the plasma membrane targeting and the nanodomain organization of the plant SPFH protein HIR2.The Plant journal : for cell and molecular biology · 2026Article
- ZDHHC5 interacts physically and functionally with DLG1 at primary cilia and regulates ciliary length and kidney morphology.Frontiers in cell and developmental biology · 2026Article
- Article
- Molecular basis for the activation of outer dynein arms in cilia.Nature structural & molecular biology · 2025Article
- Article
- Strategies for multimodal spatiotemporal profiling of phosphorylation in cilia biology.Journal of cell science · 2025Review
- C. elegans: An elegant experimental system for the study of cilia biology.Seminars in cell & developmental biology · 2025Review
- Senior-Loken Syndrome: Ocular Perspectives on Genetics, Pathogenesis, and Management.Biomolecules · 2025Review
- NEK8, a NIMA-family protein kinase at the core of the ciliary INV complex.Cell communication and signaling : CCS · 2025Review
- PSKH1 kinase activity is differentially modulated via allosteric binding of CaProceedings of the National Academy of Sciences of the United States of America · 2025Article
- Myristoylated Neuronal Calcium Sensor-1 captures the preciliary vesicle at distal appendages.eLife · 2025Article
- Vinblastine Resistance Is Associated with Nephronophthisis 3-Mediated Primary Cilia via Intraflagellar Transport Protein 88 and Apoptosis-Antagonizing Transcription Factor.International journal of molecular sciences · 2024Article
- ARL3 GTPases facilitate ODA16 unloading from IFT in motile cilia.Science advances · 2024Article
- Emerging mechanistic understanding of cilia function in cellular signalling.Nature reviews. Molecular cell biology · 2024Review
- Molecular and structural perspectives on protein trafficking to the primary cilium membrane.Biochemical Society transactions · 2024Review
- Transport and barrier mechanisms that regulate ciliary compartmentalization and ciliopathies.Nature reviews. Nephrology · 2024Review
86 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
The membrane of the primary cilium is a highly specialized compartment that organizes proteins to achieve spatially ordered signaling. Disrupting ciliary organization leads to diseases called ciliopathies, with phenotypes ranging from retinal degeneration and cystic kidneys to neural tube defects. How proteins are selectively transported to and organized in the primary cilium remains unclear. Using a proteomic approach, we identified the ARL3 effector UNC119 as a binding partner of the myristoylated ciliopathy protein nephrocystin-3 (NPHP3). We mapped UNC119 binding to the N-terminal 200 residues of NPHP3 and found the interaction requires myristoylation. Creating directed mutants predicted from a structural model of the UNC119-myristate complex, we identified highly conserved phenylalanines within a hydrophobic β sandwich to be essential for myristate binding. Furthermore, we found that binding of ARL3-GTP serves to release myristoylated cargo from UNC119. Finally, we showed that ARL3, UNC119b (but not UNC119a), and the ARL3 GAP Retinitis Pigmentosa 2 (RP2) are required for NPHP3 ciliary targeting and that targeting requires UNC119b myristoyl-binding activity. Our results uncover a selective, membrane targeting GTPase cycle that delivers myristoylated proteins to the ciliary membrane and suggest that other myristoylated proteins may be similarly targeted to specialized membrane domains.
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