Munc18b regulates core SNARE complex assembly and constitutive exocytosis by interacting with the N-peptide and the closed-conformation C-terminus of syntaxin 3.
Summary of "Munc18b regulates core SNARE complex assembly and constitutive exocytosis by interacting with the N-peptide and the closed-conformation C-terminus of syntaxin 3."
The interaction between Sec1/Munc18 (SM) and SNARE proteins constitutes the core eukaryotic membrane fusion machinery which manages exocytosis by mediating fusion of constitutively exocytic vesicles with the plasma membrane. However, mechanistic details on the nature and the physiologic impact of SM/SNARE interactions remain largely elusive. Detailed characterization of the interaction profiles between Munc18b and its cognate SNAREs, Syntaxin 3, SNAP-23 and VAMP8, revealed that Munc18b binds Syntaxin 3, VAMP8 and the assembled core SNARE complex consisting of Synaxin 3, SNAP-23 and VAMP8. Dissection of the Munc18b/Stx3 heterodimer suggested that Munc18b interacts with Stx3's conserved N-peptide as well as with its closed-conformation C-terminus encompassing the Habc domain, a linker and the SNARE (H3) motif. Deletion of the Habc domain or mutations interrupting the intramolecular binding of the Habc and H3 domains abrogated the Munc18b/Stx3 interaction. Although only the N-peptide deletion mutant but not the soluble wild-type Stx3 is assembled into the core SNARE complex in the presence of Munc18b in vitro, ectopic expression of this SM protein increases constitutive exocytosis in mammalian cells. Our results suggest that Munc18b is functionally coupled to the assembly of exocytic SNARE complexes and increases exocytosis by interacting with the N-peptide and closed-conformation C-terminus of Stx3 thereby neutralizing the secretion-inhibitory effect of this SNARE.
Affiliation
Journal Details
This article was published in the following journal.
Name: The Biochemical journal
ISSN: 1470-8728
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20695848
- DOI: http://dx.doi.org/10.1042/BJ20100145
Medical and Biotech [MESH] Definitions
Synaptosomal-associated Protein 25
A ubiquitous target SNARE protein that interacts with SYNTAXIN and SYNAPTOBREVIN. It is a core component of the machinery for intracellular MEMBRANE FUSION. The sequence contains 2 SNARE domains, one is the prototype for the Qb-SNARES, and the other is the prototype for the Qc-SNARES.
Q-snare Proteins
SNARE proteins in which the central amino acid residue of the SNARE motif is a GLUTAMINE. They are classified separately from the R-SNARE PROTEINS where the central amino acid residue of the SNARE motif is an ARGININE. Subfamilies, the QA-SNARES; QB-SNARES; and QC-SNARES are grouped by the position of their SNARE motif-containing-domains in the SNARE complex and by their sequence similarities.
Syntaxin 1
A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.
Qc-snare Proteins
A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the C-terminal SNARE domain of SNAP-25 and which also are most similar to the C-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.
Qb-snare Proteins
A subfamily of Q-SNARE PROTEINS which occupy the same position in the SNARE complex as the N-terminal SNARE domain of SNAP-25 and which also are most similar to the N-terminal region of SNAP-25 in their AMINO ACID SEQUENCE.
PubMed Articles
Neuropeptide and peptide hormone secretion from neural and endocrine cells occurs by Ca(2+)-triggered dense-core vesicle exocytosis. The membrane fusion machinery consisting of vesicle and plasma memb...
{alpha}-Synuclein Promotes SNARE-Complex Assembly in Vivo and in Vitro.
Presynaptic nerve terminals release neurotransmitters repeatedly, often at high frequency, and in relative isolation from neuronal cell bodies. Repeated release requires cycles of SNARE-complex assemb...
The t-SNARE Complex: A Close Up.
The SNARE proteins, syntaxin, SNAP-25, and synaptobrevin have long been known to provide the driving force for vesicle fusion in the process of regulated exocytosis. Of particular interest is the init...
Airway mucin secretion and mast cell degranulation must be tightly controlled for homeostasis of the lungs and immune system, respectively. We found the exocytic protein Munc18b highly expressed in mo...
CAPS (aka CADPS) is required for optimal vesicle exocytosis in neurons and endocrine cells where it functions to prime the exocytic machinery for Ca(2+)-triggered fusion. Fusion is mediated by trans c...
Clinical Trials
Prospective Randomized Comparison of Cold Snare Polypectomy and Conventional Polypectomy
The aim of this study is to compare cold snare polypectomy and conventional polypectomy for the removal and retrieval of small colorectal polyps. Cold snare polypectomy for colorectal pol...
The Mechanism of Melanocyte Self-Assembly on Biomaterials and the Functional Analysis
The aim of this study is to survey melanocytes in the ability of self-assembly on biomaterials and functional analysis in vitro. Also, this study may provide a better way for treatment of...
Data Analyses for Ancillary WISE Femhrt Hormone Replacement Study
For the purposes of this study, as a core lab coordinating center, the investigators will be performing P31 MRS core lab analyses; hormone core lab analyses; lipid core lab analyses; gluco...
The purpose of this investigation is to determine the relationship of core stability to core proprioception
A Study to Evaluate the Use of Stavudine (d4T) to Treat AIDS Dementia Complex
The purpose of this study is to see if adding stavudine (d4T) to anti-HIV drug regimens (with or without zidovudine, ZDV) can improve symptoms of AIDS Dementia Complex (ADC, problems invol...
