ArticleDevelopmental cell2023
The ancestral ESCRT protein TOM1L2 selects ubiquitinated cargoes for retrieval from cilia.
Article in Developmental cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 30 citations in OpenAlex.
- Primary cilia: master conductors of cellular communication in development and disease.Nature reviews. Nephrology · 2026Review
- K63-linked ubiquitin chains mark inactive Smoothened for packaging into ciliary extracellular vesicles.bioRxiv : the preprint server for biology · 2026Article
- Article
- Integrative Proteomic Analysis Reveals VMG Oncolytic Virus-Induced Molecular Reprogramming in Pancreatic Ductal Adenocarcinoma.Research square · 2026Article
- Bardet-Biedl syndrome 1 mutations differentially impact BBSome integrity and ciliary trafficking.Cell communication and signaling : CCS · 2026Article
- In situ proteomics unveils specialized domains for extrasynaptic signaling on neuronal cilia.Science advances · 2026Article
- BBSome: An essential component of hypothalamic regulation of energy homeostasis.Reviews in endocrine & metabolic disorders · 2026Review
- TOM1 family proteins: from cargo sorting to immune dysregulation and cancer.Cell communication and signaling : CCS · 2026Review
- ZDHHC5 interacts physically and functionally with DLG1 at primary cilia and regulates ciliary length and kidney morphology.Frontiers in cell and developmental biology · 2026Article
- A Histone Deacetylase Activity Model for the Discovery and Validation of Sepsis Biomarkers.Endocrine, metabolic & immune disorders drug targets · 2026Article
- Article
- Advances in ciliary proteomics - towards cracking the hidden proteome code of cilia.Journal of cell science · 2025Review
- Identification of novel interacting proteins of FUZ and GPR161.bioRxiv : the preprint server for biology · 2025Article
- Cilia.Pro database of ciliary proteins from vertebrates,Molecular biology of the cell · 2025Article
- BBSome-Mediated Clearance of Ubiquitinated IMPG2 Defines a Constitutive Ciliary Retrieval Pathway in Photoreceptors.bioRxiv : the preprint server for biology · 2025Article
- FGFR2 residence in primary cilia is necessary for epithelial cell signaling.The Journal of cell biology · 2025Article
- Sensory stimuli and cilium trafficking defects trigger the release of ciliary extracellular vesicles from multiple ciliary locations.bioRxiv : the preprint server for biology · 2025Article
- The intraflagellar transport cycle.Nature reviews. Molecular cell biology · 2025Review
- Tonic ubiquitination of the central body weight regulator melanocortin receptor 4 (MC4R) promotes its constitutive exit from cilia.PLoS biology · 2025Article
- GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.PLoS biology · 2024Article
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
Many G protein-coupled receptors (GPCRs) reside within cilia of mammalian cells and must undergo regulated exit from cilia for the appropriate transduction of signals such as hedgehog morphogens. Lysine 63-linked ubiquitin (UbK63) chains mark GPCRs for regulated removal from cilia, but the molecular basis of UbK63 recognition inside cilia remains elusive. Here, we show that the BBSome-the trafficking complex in charge of retrieving GPCRs from cilia-engages the ancestral endosomal sorting factor target of Myb1-like 2 (TOM1L2) to recognize UbK63 chains within cilia of human and mouse cells. TOM1L2 directly binds to UbK63 chains and the BBSome, and targeted disruption of the TOM1L2/BBSome interaction results in the accumulation of TOM1L2, ubiquitin, and the GPCRs SSTR3, Smoothened, and GPR161 inside cilia. Furthermore, the single-cell alga Chlamydomonas also requires its TOM1L2 ortholog in order to clear ubiquitinated proteins from cilia. We conclude that TOM1L2 broadly enables the retrieval of UbK63-tagged proteins by the ciliary trafficking machinery.
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Registered trials
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 Socratic graph.