ArticleNature communications2016
PDE6δ-mediated sorting of INPP5E into the cilium is determined by cargo-carrier affinity.
Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
54 citing papers in PubMed.
- The EH-binding protein EHBP1 operates in a ciliary functional module affected by INPP5E dysfunction.Journal of cell science · 2026Article
- K-Ras controls asymmetric cell divisions from the primary cilium.Cell death & disease · 2026Article
- Development of a Genetically Encoded and Potent PDE6D Inhibitor.Chembiochem : a European journal of chemical biology · 2025Article
- Drugging Ras trafficking-are there new roads to travel?npj drug discovery · 2025Review
- Protein lipidation in the tumor microenvironment: enzymology, signaling pathways, and therapeutics.Molecular cancer · 2025Review
- A novel recurrent ARL3 variant c.209G > A p.(Gly70Glu) causes variable non-syndromic dominant retinal dystrophy with defective lipidated protein transport in human retinal stem cell models.Human molecular genetics · 2025Article
- Regulation of INPP5E in Ciliogenesis, Development, and Disease.International journal of biological sciences · 2025Review
- An Improved PDE6D Inhibitor Combines with Sildenafil To InhibitJournal of medicinal chemistry · 2024Article
- Transport and barrier mechanisms that regulate ciliary compartmentalization and ciliopathies.Nature reviews. Nephrology · 2024Review
- INPP5E regulates CD3ζ enrichment at the immune synapse by phosphoinositide distribution control.Communications biology · 2023Article
- Phosphoinositides in New Spaces.Cold Spring Harbor perspectives in biology · 2023Review
- Article
- Disrupting the ciliary gradient of active Arl3 affects rod photoreceptor nuclear migration.eLife · 2023Article
- Recent advances in the understanding of cilia mechanisms and their applications as therapeutic targets.Frontiers in molecular biosciences · 2023Review
- ARL3 mediates BBSome ciliary turnover by promoting its outward movement across the transition zone.The Journal of cell biology · 2022Article
- Article
- Phylogenetic profiling and cellular analyses of ARL16 reveal roles in traffic of IFT140 and INPP5E.Molecular biology of the cell · 2022Article
- Stabilization of the RAS:PDE6D Complex Is a Novel Strategy to Inhibit RAS Signaling.Journal of medicinal chemistry · 2022Article
- The ARF GAPs ELMOD1 and ELMOD3 act at the Golgi and cilia to regulate ciliogenesis and ciliary protein traffic.Molecular biology of the cell · 2022Article
- Cilia-Localized Counterregulatory Signals as Drivers of Renal Cystogenesis.Frontiers in molecular biosciences · 2022Review
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
The phosphodiesterase 6 delta subunit (PDE6δ) shuttles several farnesylated cargos between membranes. The cargo sorting mechanism between cilia and other compartments is not understood. Here we show using the inositol polyphosphate 5'-phosphatase E (INPP5E) and the GTP-binding protein (Rheb) that cargo sorting depends on the affinity towards PDE6δ and the specificity of cargo release. High-affinity cargo is exclusively released by the ciliary transport regulator Arl3, while low-affinity cargo is released by Arl3 and its non-ciliary homologue Arl2. Structures of PDE6δ/cargo complexes reveal the molecular basis of the sorting signal which depends on the residues at the -1 and -3 positions relative to farnesylated cysteine. Structure-guided mutation allows the generation of a low-affinity INPP5E mutant which loses exclusive ciliary localization. We postulate that the affinity to PDE6δ and the release by Arl2/3 in addition to a retention signal are the determinants for cargo sorting and enrichment at its destination.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.