ArticleMolecular biology of the cell2011
A conserved signal and GTPase complex are required for the ciliary transport of polycystin-1.
Article in Molecular biology of the cell, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 107 citations in OpenAlex.
- GRAF1-dependent endocytotic processes and the Golgi apparatus contribute to previously unrecognized intermediate stages of early ciliogenesis.Nature communications · 2026Article
- Rab8 and TNPO1 function as the ciliary transport adapters for GPCRs.The Journal of biological chemistry · 2026Article
- Physiologic mechanisms underlying polycystic kidney disease.Physiological reviews · 2025Review
- A tale of Rabs and the exocyst complex in ciliary trafficking and biogenesis.Frontiers in cell and developmental biology · 2025Review
- Article
- Molecular and structural perspectives on protein trafficking to the primary cilium membrane.Biochemical Society transactions · 2024Review
- Algal rhodopsins encoding diverse signal sequence holds potential for expansion of organelle optogenetics.Biophysics and physicobiology · 2023Article
- Phylogenetic profiling and cellular analyses of ARL16 reveal roles in traffic of IFT140 and INPP5E.Molecular biology of the cell · 2022Article
- Cilia-Localized Counterregulatory Signals as Drivers of Renal Cystogenesis.Frontiers in molecular biosciences · 2022Review
- The GPCR properties of polycystin-1- A new paradigm.Frontiers in molecular biosciences · 2022Review
- The ins and outs of the Arf4-based ciliary membrane-targeting complex.Small GTPases · 2021Review
- On the Wrong Track: Alterations of Ciliary Transport in Inherited Retinal Dystrophies.Frontiers in cell and developmental biology · 2021Review
- A genetic screen in Drosophila reveals an unexpected role for the KIP1 ubiquitination-promoting complex in male fertility.PLoS genetics · 2020Article
- Cross-Kingdom Activation ofJournal of bacteriology · 2020Review
- ARF family GTPases with links to cilia.American journal of physiology. Cell physiology · 2020Review
- Regulation of polycystin expression, maturation and trafficking.Cellular signalling · 2020Review
- Ciliary exclusion of Polycystin-2 promotes kidney cystogenesis in an autosomal dominant polycystic kidney disease model.Nature communications · 2019Article
- Protein phosphatase 1α interacts with a novel ciliary targeting sequence of polycystin-1 and regulates polycystin-1 trafficking.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- A Ciliary View of the Immunological Synapse.Cells · 2019Review
- A global analysis of IFT-A function reveals specialization for transport of membrane-associated proteins into cilia.Journal of cell science · 2019Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 1 country.
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Abstract
Primary cilia regulate epithelial differentiation and organ function. Failure of mutant polycystins to localize to cilia abolishes flow-stimulated calcium signaling and causes autosomal dominant polycystic kidney disease. We identify a conserved amino acid sequence, KVHPSST, in the C-terminus of polycystin-1 (PC1) that serves as a ciliary-targeting signal. PC1 binds a multimeric protein complex consisting of several GTPases (Arf4, Rab6, Rab11) and the GTPase-activating protein (GAP), ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 (ASAP1) in the Golgi, which facilitates vesicle budding and Golgi exocytosis. A related N-terminal ciliary-targeting sequence in polycystin-2 similarly binds Arf4. Deletion of the extreme C-terminus of PC1 ablates Arf4 and ASAP1 binding and prevents ciliary localization of an integral membrane CD16.7-PC1 chimera. Interactions are confirmed for chimeric and endogenous proteins through quantitated in vitro and cell-based approaches. PC1 also complexes with Rab8; knockdown of trafficking regulators Arf4 or Rab8 functionally blocks CD16.7-PC1 trafficking to cilia. Mutations in rhodopsin disrupt a similar signal and cause retinitis pigmentosa, while Bardet-Biedl syndrome, primary open-angle glaucoma, and tumor cell invasiveness are linked to dysregulation of ASAP1 or Rab8 or its effectors. In this paper, we provide evidence for a conserved GTPase-dependent ciliary-trafficking mechanism that is shared between epithelia and neurons, and is essential in ciliary-trafficking and cell homeostasis.
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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.