ArticleCurrent biology : CB2016
Retromer Endosome Exit Domains Serve Multiple Trafficking Destinations and Regulate Local G Protein Activation by GPCRs.
Article in Current biology : CB, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 65 citations in OpenAlex.
- GPCR-selective effects of endocytosis on cellular signaling through the cAMP/PKA cascade.The Journal of biological chemistry · 2026Article
- Hybrid endosomal coats contain different classes of sorting nexins.The EMBO journal · 2026Article
- Lysosomal down-regulation of the mu opioid receptor is opposed by the Retromer complex.Science advances · 2026Article
- Arrestin-3 sca-olds multiple MAP3Ks driving stress-induced JNK3 activation and cell death.bioRxiv : the preprint server for biology · 2026Article
- Mapping of endosomal proximity proteomes reveals Retromer as a hub for RAB GTPase regulation.Nature communications · 2025Article
- Opioid receptors reveal a discrete cellular mechanism of endosomal G protein activation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Intersection of GPCR trafficking and cAMP signaling at endomembranes.The Journal of cell biology · 2025Review
- An engineered trafficking biosensor reveals a role for DNAJC13 in DOR downregulation.Nature chemical biology · 2025Article
- The β2 adrenergic receptor cross-linked interactome identifies 14-3-3 proteins as regulating the availability of signaling-competent receptors.Molecular pharmacology · 2025Article
- Assembly and fission of tubular carriers mediating protein sorting in endosomes.Nature reviews. Molecular cell biology · 2024Review
- Mechanism and regulation of cargo entry into the Commander endosomal recycling pathway.Nature communications · 2024Article
- cAMP signaling: a remarkably regional affair.Trends in biochemical sciences · 2024Review
- Endosome positioning coordinates spatially selective GPCR signaling.Nature chemical biology · 2024Article
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- Article
- The role of Evi/Wntless in exporting Wnt proteins.Development (Cambridge, England) · 2023Review
- The needs of a synapse-How local organelles serve synaptic proteostasis.The EMBO journal · 2022Review
- SNX27-Retromer directly binds ESCPE-1 to transfer cargo proteins during endosomal recycling.PLoS biology · 2022Article
- Mechanisms for Regulating and Organizing Receptor Signaling by Endocytosis.Annual review of biochemistry · 2021Review
- Proteomic Approaches to Investigate Regulated Trafficking and Signaling of G Protein-Coupled Receptors.Molecular pharmacology · 2021Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Retromer mediates sequence-directed cargo exit from endosomes to support both endosome-to-Golgi (retrograde transport) and endosome-to-plasma membrane (recycling) itineraries. It is not known whether these trafficking functions require cargos to exit endosomes separately via distinct transport intermediates or whether the same retromer-coated carriers can support both itineraries. We addressed this question by comparing human Wntless (Wls) and β2 adrenergic receptor (β2AR), which require retromer physiologically for retrograde transport and recycling, respectively. We show here by direct visualization in living cells that both cargos transit primarily the same endosomes and exit via shared transport vesicles generated from a retromer-coated endosome domain. While both Wls and β2AR clearly localize to the same retromer-coated endosome domains, Wls is consistently enriched more strongly. This enrichment difference is determined by distinct motifs present in the cytoplasmic tail of each cargo, with Wls using tandem Φ-X-[L/M] motifs and β2AR using a PDZ motif. Exchanging these determinants reverses the enrichment phenotype of each cargo but does not change cargo itinerary, verifying the multifunctional nature of retromer and implying that additional sorting must occur downstream. Quantitative differences in the degree of cargo enrichment instead underlie a form of kinetic sorting that impacts the rate of cargo delivery via both itineraries and determines the ability of β2AR to activate its cognate G protein transducer locally from endosomes. We propose that mammalian retromer forms a multifunctional membrane coat that supports shared cargo exit for divergent trafficking itineraries and regulates signaling from endosomes.
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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 OpenQuestion graph.