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ComplexinII (CpxII) inhibits non-synchronized vesicle fusion, but the underlying mechanisms have remained unclear. Here, we provide evidence that the far C-terminal domain (CTD) of CpxII interferes with SNARE assembly, thereby arresting tonic exocytosis. Acute infusion of a CTD-derived peptide into mouse chromaffin cells enhances synchronous release by diminishing premature vesicle fusion like full-length CpxII, indicating a direct, inhibitory function of the CTD that sets the magnitude of the primed vesicle pool. We describe a high degree of structural similarity between the CpxII CTD and the SNAP25-SN1 domain (C-terminal half) and show that the CTD peptide lowers the rate of SDS-resistant SNARE complex formation in vitro. Moreover, corresponding CpxII:SNAP25 chimeras do restore complexin's function and even 'superclamp' tonic secretion. Collectively, these results support a so far unrecognized clamping mechanism wherein the CpxII C-terminus hinders spontaneous SNARE complex assembly, enabling the build-up of a release-ready pool of vesicles for synchronized Ca2+-triggered exocytosis.
Pubmed ID: 30044227
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Digital image processing system where microscope settings and processing steps may be adjusted in single user interface. Can acquire images from variety of cameras. Includes software package for capturing, archiving and preparing images for publication. Allows users to visualize and present images in several dimensions. Functionality of imaging toolbox expands constantly with wide range of different modules that are tailored to specific applications or microscope accessories. This resource is duplicated by SCR_018376
View all literature mentionsStatistical analysis and scientific graphing software for Windows OS.
View all literature mentionsSoftware analysis package for molecular biology community. Automatically copes with data in variety of formats and allows transparent retrieval of sequence data from web. Libraries are provided with package. Provides toolkit for creating bioinformatics applications or workflows. Provides set of sequence analysis programs. Provided programs cover areas such as sequence alignment, rapid database searching with sequence patterns, protein motif identification, nucleotide sequence pattern analysis, codon usage analysis for small genomes, rapid identification of sequence patterns in large scale sequence sets, and presentation tools for publication.
View all literature mentionsCell line BHK-21 is a Spontaneously immortalized cell line with a species of origin Mesocricetus auratus (Golden hamster)
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