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.
This article was published in the following journal.
Name: The Biochemical journal
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.
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.
A neuronal cell membrane protein that combines with SNAP-25 and SYNAPTOBREVIN 2 to form a SNARE complex that leads to EXOCYTOSIS.
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.
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.
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