ArticleMolecular biology of the cell2003
Membrane targeting of Rab GTPases is influenced by the prenylation motif.
Article in Molecular biology of the cell, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 83 papers.
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Who cites it
83 citing papers in PubMed, 154 citations in OpenAlex.
- Loss of bronchoprotection with ICS plus LABA treatment, β-receptor dynamics, and the effect of alendronate.The Journal of allergy and clinical immunology · 2019Trial
- Geranylgeranylation is required for B-cell proliferation and plasma cell survival implications for autoimmune therapy.Cellular & molecular immunology · 2026Article
- Farnesol and geranylgeraniol in plant reproduction: insights from Arabidopsis and beyond.Journal of experimental botany · 2026Review
- Host prenylation promotes membrane association of theMicrobiology (Reading, England) · 2026Article
- Lipopolysaccharide stimulates dynamic changes in B cell metabolism to promote proliferation.eLife · 2026Article
- Rab27a-mediated exosome secretion facilitates classical swine fever virus release and immune evasion.Journal of virology · 2025Article
- Uncovering protein prenylation in Th1 cells: novel prenylation sites and insights into statin and farnesyltransferase inhibition.BMC biology · 2025Article
- Structure-activity relationship of isoprenoid triazole bisphosphonate-based geranylgeranyl diphosphate synthase inhibitors: Effects on pharmacokinetics, biodistribution, and hepatic transporters.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
- Geranylgeranyl diphosphate synthase inhibition impairs osteoclast differentiation, morphology, and resorptive activity.JBMR plus · 2025Article
- Functional characterization and phenotyping of RAB2A and Lactadherin/MFGE8 as boar sperm zona pellucida binding proteins.Frontiers in cell and developmental biology · 2025Article
- Unexpected inhibition of the lipid kinase PIKfyve reveals an epistatic role for p38 MAPKs in endolysosomal fission and volume control.Cell death & disease · 2024Article
- Salmonella engages CDC42 effector protein 1 for intracellular invasion.Journal of cellular physiology · 2024Article
- RAB1A haploinsufficiency phenocopies the 2p14-p15 microdeletion and is associated with impaired neuronal differentiation.American journal of human genetics · 2023Article
- Evaluation of geranylgeranyl diphosphate synthase inhibition as a novel strategy for the treatment of osteosarcoma and Ewing sarcoma.Drug development research · 2023Article
- External stimulation induces the secretion of autophagosome-like vesicles by B cells.Autophagy reports · 2023Article
- Targeting the Isoprenoid Biosynthetic Pathway in Multiple Myeloma.International journal of molecular sciences · 2022Review
- Atorvastatin Enhances the Efficacy of Immune Checkpoint Therapy and Suppresses the Cellular and Extracellular Vesicle PD-L1.Pharmaceutics · 2022Article
- A peptide derived from the N-terminus of charged multivesicular body protein 6 (CHMP6) promotes the secretion of gene editing proteins via small extracellular vesicle production.Bioengineered · 2022Article
- Geranylgeranyl diphosphate synthase inhibitor and proteasome inhibitor combination therapy in multiple myeloma.Experimental hematology & oncology · 2022Article
- The Rab Geranylgeranyl Transferase Beta Subunit Is Essential for Embryo and Seed Development inInternational journal of molecular sciences · 2021Article
23 more citing papers are in PubMed but not listed here.
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7 authors at 1 institution in 1 country.
Funding
Abstract
Rab GTPases are regulators of membrane traffic. Rabs specifically associate with target membranes via the attachment of (usually) two geranylgeranyl groups in a reaction involving Rab escort protein and Rab geranylgeranyl transferase. In contrast, related GTPases are singly prenylated by CAAX prenyl transferases. We report that di-geranylgeranyl modification is important for targeting of Rab5a and Rab27a to endosomes and melanosomes, respectively. Transient expression of EGFP-Rab5 mutants containing two prenylatable cysteines (CGC, CC, CCQNI, and CCA) in HeLa cells did not affect endosomal targeting or function, whereas mono-cysteine mutants (CSLG, CVLL, or CVIM) were mistargeted to the endoplasmic reticulum (ER) and were nonfunctional. Similarly, Rab27aCVLL mutant is also mistargeted to the ER and transgenic expression on a Rab27a null background (Rab27aash) did not rescue the coat color phenotype, suggesting that Rab27aCVLL is not functional in vivo. CAAX prenyl transferase inhibition and temperature-shift experiments further suggest that Rabs, singly or doubly modified are recruited to membranes via a Rab escort protein/Rab geranylgeranyl transferase-dependent mechanism that is distinct from the insertion of CAAX-containing GTPases. Finally, we show that both singly and doubly modified Rabs are extracted from membranes by RabGDIalpha and propose that the mistargeting of Rabs to the ER results from loss of targeting information.
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