Rapid and efficient synaptic vesicle fusion requires a pool of primed vesicles, the nearby tethering of Ca2+ channels, and the presence of the phospholipid PIP2 in the target membrane. Although the presynaptic active zone mediates the first two requirements, it is unclear how fusion is targeted to membranes with high PIP2 content. Here we find that the C2B domain of the active zone scaffold RIM is critical for action potential-triggered fusion. Remarkably, the known RIM functions in vesicle priming and Ca2+ influx do not require RIM C2B domains. Instead, biophysical experiments reveal that RIM C2 domains, which lack Ca2+ binding, specifically bind to PIP2. Mutational analyses establish that PIP2 binding to RIM C2B and its tethering to the other RIM domains are crucial for efficient exocytosis. We propose that RIM C2B domains are constitutive PIP2-binding modules that couple mechanisms for vesicle priming and Ca2+ channel tethering to PIP2-containing target membranes.
Pubmed ID: 29606581 RIS Download
Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.
Software program that can illustrate the output of SEDFIT and SEDPHAT programs and can perform simple calculations with the data. It is designed to work with sedimentation velocity, sedimentation equilibrium, ITC, DLS, and isotherm data.
View all literature mentionsThis polyclonal targets VGAT (cytoplasmic domain)
View all literature mentionsThis unknown targets Bassoon mAb (SAP7F407)
View all literature mentionsThis polyclonal targets Synaptophysin 1
View all literature mentionsThis monoclonal targets Mouse Rim Clone 26
View all literature mentionsThis monoclonal targets Munc 13-1
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis unknown targets
View all literature mentionsThis monoclonal targets Cavbeta4 calcium channel
View all literature mentionsThis polyclonal targets RIM1 central domains
View all literature mentionsMus musculus with name STOCK Rims1tm3Sud/J from IMSR.
View all literature mentionsMus musculus with name STOCK Rims2tm1.1Sud/J from IMSR.
View all literature mentionsPublic academic health science center in Dallas, Texas.
View all literature mentionsOpen source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.
View all literature mentionsMulti paradigm numerical computing environment and fourth generation programming language developed by MathWorks. Allows matrix manipulations, plotting of functions and data, implementation of algorithms, creation of user interfaces, and interfacing with programs written in other languages, including C, C++, Java, Fortran and Python. Used to explore and visualize ideas and collaborate across disciplines including signal and image processing, communications, control systems, and computational finance.
View all literature mentionsCell line HEK293T is a Transformed cell line with a species of origin Homo sapiens (Human)
View all literature mentionsMus musculus with name STOCK Rims2tm1.1Sud/J from IMSR.
View all literature mentionsMus musculus with name STOCK Rims1tm3Sud/J from IMSR.
View all literature mentions