ArticleThe Journal of biological chemistry2016
Munc13-4 Is a Rab11-binding Protein That Regulates Rab11-positive Vesicle Trafficking and Docking at the Plasma Membrane.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 69 citations in OpenAlex.
- Munc13-4-STX7 inhibitors impair endosomal TLR activation and systemic inflammation.Nature chemical biology · 2026Article
- Distinct Rab11-associated membrane trafficking pathways bidirectionally control neuronal extracellular vesicle cargo traffic.bioRxiv : the preprint server for biology · 2026Article
- Article
- Nexinhib20 inhibits JFC1-mediated mobilization of a subset of CD11b/CD18+ vesicles decreasing integrin avidity, but does not inhibit Rac1.Journal of leukocyte biology · 2025Article
- Engineered Extracellular Vesicles as a New Class of Nanomedicine.Chem & bio engineering · 2025Review
- Recycling machinery of integrin coupled with focal adhesion turnover via RAB11-UNC13D-FAK axis for migration of pancreatic cancer cells.Journal of translational medicine · 2024Article
- Defective endomembrane dynamics in Rab27a deficiency impairs nucleic acid sensing and cytokine secretion in immune cells.Cell reports · 2024Article
- The link between intracellular calcium signaling and exosomal PD-L1 in cancer progression and immunotherapy.Genes & diseases · 2024Review
- Functional role of UNC13D in immune diseases and its therapeutic applications.Frontiers in immunology · 2024Review
- Reconstitution of Rab11-FIP4 Expression Rescues Cellular Homeostasis in Cystinosis.Molecular and cellular biology · 2024Article
- Murine Models of Familial Cytokine Storm Syndromes.Advances in experimental medicine and biology · 2024Review
- Cytokine Storm Syndrome Associated with Systemic Juvenile Idiopathic Arthritis.Advances in experimental medicine and biology · 2024Review
- Differences between migrasome, a 'new organelle', and exosome.Journal of cellular and molecular medicine · 2023Review
- The biogenesis and secretion of exosomes and multivesicular bodies (MVBs): Intercellular shuttles and implications in human diseases.Genes & diseases · 2023Review
- CaAdvances in experimental medicine and biology · 2023Article
- Article
- Differential dysregulation of granule subsets in WASH-deficient neutrophil leukocytes resulting in inflammation.Nature communications · 2022Article
- Roles of neutrophil granule proteins in orchestrating inflammation and immunity.The FEBS journal · 2022Review
- DYNC1LI2 regulates localization of the chaperone-mediated autophagy receptor LAMP2A and improves cellular homeostasis in cystinosis.Autophagy · 2022Article
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The small GTPase Rab11 and its effectors control trafficking of recycling endosomes, receptor replenishment and the up-regulation of adhesion and adaptor molecules at the plasma membrane. Despite recent advances in the understanding of Rab11-regulated mechanisms, the final steps mediating docking and fusion of Rab11-positive vesicles at the plasma membrane are not fully understood. Munc13-4 is a docking factor proposed to regulate fusion through interactions with SNAREs. In hematopoietic cells, including neutrophils, Munc13-4 regulates exocytosis in a Rab27a-dependent manner, but its possible regulation of other GTPases has not been explored in detail. Here, we show that Munc13-4 binds to Rab11 and regulates the trafficking of Rab11-containing vesicles. Using a novel Time-resolved Fluorescence Resonance Energy Transfer (TR-FRET) assay, we demonstrate that Munc13-4 binds to Rab11a but not to dominant negative Rab11a. Immunoprecipitation analysis confirmed the specificity of the interaction between Munc13-4 and Rab11, and super-resolution microscopy studies support the interaction of endogenous Munc13-4 with Rab11 at the single molecule level in neutrophils. Vesicular dynamic analysis shows the common spatio-temporal distribution of Munc13-4 and Rab11, while expression of a calcium binding-deficient mutant of Munc13-4 significantly affected Rab11 trafficking. Munc13-4-deficient neutrophils showed normal endocytosis, but the trafficking, up-regulation, and retention of Rab11-positive vesicles at the plasma membrane was significantly impaired. This correlated with deficient NADPH oxidase activation at the plasma membrane in response to Rab11 interference. Our data demonstrate that Munc13-4 is a Rab11-binding partner that regulates the final steps of Rab11-positive vesicle docking at the plasma membrane.
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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.