Protein trafficking
How does monoubiquitin turn down Rab5?
Open access · cc by · source: Europe PMC
Rab5 is monoubiquitinated at specific lysines; ubiquitin at K140/K165 disrupts effector binding and downregulates endocytic trafficking.
Study at a glance
- Design
- Animal / in-vitro — Mapped Rab5 monoubiquitination sites and tested chemically monoubiquitinated Rab5 function
- N
- Cell-biochemistry of Rab5 ubiquitin sites K116/K140/K165 — no single sample N
- Population
- Cultured cells expressing Rab5 variants
- Outcome
- Site-specific monoubiquitination downregulating Rab5 endocytic signaling
Structured fields used in claim comparison tables when every cited study has a complete layer.
Key findings
Rab5 is monoubiquitinated at K116, K140, and K165; K140/K165 modifications downregulate the Rab5 endocytic pathway via disrupted partners and nucleotide conversion, while K116 has little localization effect.
Methodology
Mapped Rab5 monoubiquitination sites in cultured cells, built chemically monoubiquitinated Rab5, and tested structure, nucleotide handling, effector binding, and endosome localization.
Limitations
Does not identify the endogenous E3 ligase or fully map in vivo tissue roles of each site.
How this study connects
Role on claims
Each row is a claim on a concept or method page where this paper supports, challenges, or qualifies the statement. Roles are hand-checked — not a model guess.
Multiple empirical papers in this library examine protein trafficking with mechanistic biological findings.
Evidence for the claim as stated.
Rab5 is monoubiquitinated at K116, K140, and K165; K140/K165 modifications downregulate the Rab5 endocytic pathway via disrupted partners and nucleotide conversion, while K116 has little localization effect.
Evidence for the claim as stated.
Systems and scales differ across protein trafficking studies (species, tissues, methods), so mechanisms should not be over-generalised.
Evidence for the claim as stated.
USP8 is required for Hedgehog-induced Smoothened surface accumulation and keeps Smo out of Rab5 early endosomes. Site-specific monoubiquitination of Rab5 at K140 and K165 (not K116) downregulates the endocytic pathway via disrupted effectors and nucleotide conversion. Both papers use localisation of Smo or Rab5 as a trafficking IF readout.
Evidence for the claim as stated.
IF is a screening camera in Vero cells (berzosertib 100 nM, 48 hpi), a tissue census in TB lung (35 patients), a trafficking assay for Smo/Rab5/spike, and a polarity assay in enteroids. 'Positive staining' in a drug screen is not the same claim as PD-1 on human tissue-resident T cells or as K140/K165 moving Rab5 off endosomes.
Evidence for the claim as stated.
Rab5 monoubiquitination sites were mapped at K116, K140 and K165; chemically monoubiquitinated Rab5 then showed that K140/K165 downregulate the endocytic pathway via disrupted effectors and nucleotide conversion, while K116 has little localisation effect. Site-resolved MS (or MS-informed chemistry) here is a modification map, not an identification of the endogenous E3 ligase.
Evidence for the claim as stated.
Genuine MS designs still disagree about what is being counted. APEX2 inventories membrane-face neighbours in living cells (22 OMM; 72 ERM); caveolar work quantifies a purified coat; Rab5 work maps three ubiquitin lysines; rice work maps histone acylations under stress. A 'proteomics paper' can be spatial, stoichiometric, or epigenetic, and those outputs are not interchangeable.
Evidence for the claim as stated.
Open questions
Tensions this paper is part of
From concept pages' “where studies disagree.” Disagreement means the same question; scope means different assays, populations, or outcomes.
Systems and scales differ across protein trafficking studies (species, tissues, methods), so mechanisms should not be over-generalised.
- Supports · How do proteins find plasmodesmata?
- Supports · Spike glycosylation and palmitoylation trafficking
IF is a screening camera in Vero cells (berzosertib 100 nM, 48 hpi), a tissue census in TB lung (35 patients), a trafficking assay for Smo/Rab5/spike, and a polarity assay in enteroids. 'Positive staining' in a drug screen is not the same claim as PD-1 on human tissue-resident T cells or as K140/K165 moving Rab5 off endosomes.
- Supports · ATR inhibitor blocks SARS-CoV-2
- Supports · PD-1 blockade reactivates TB via TNF
- Supports · Apical-out enteroids for pathogen access
Genuine MS designs still disagree about what is being counted. APEX2 inventories membrane-face neighbours in living cells (22 OMM; 72 ERM); caveolar work quantifies a purified coat; Rab5 work maps three ubiquitin lysines; rice work maps histone acylations under stress. A 'proteomics paper' can be spatial, stoichiometric, or epigenetic, and those outputs are not interchangeable.
- Supports · Mapping the faces of mitochondria and ER
- Supports · What proteins build the caveolar coat?
- Supports · Histone acylations respond to plant stress
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