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Research Paper
Munc18: A Presynaptic Transmitter Release Site N type (CaV2.2) Calcium Channel Interacting Protein
Allen W. Chan, Rajesh Khanna, Qi Li and Elise F. Stanley
volume 1 | issue 1
January/February 2007Pages: 11 - 20
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Munc18 is a presynaptic protein that is essential for transmitter release. Recent studies have indicated that this protein is involved in secretory vesicle docking but its binding partners in this role remain a mystery. We demonstrate using the isolated calyx-type presynaptic terminal of the chick ciliary ganglion that staining for Munc18 co-localizes and covaries with that for transmitter release site N type calcium channels (CaV2.2), consistent with elements of a common release site complex. Biochemical analysis demonstrated that the protein co-precipitates with CaV2.2 from lysates of rat or chick brain, including the synaptic, long-splice variant; presynaptic terminal surface membrane proteins, and a cell line co-expressing Munc18 and CaV2.2. Munc18 bound with high affinity to the CaV2.2 II-III intracellular loop, low affinity to the I-II loop but not to other channel intracellular regions. Over-expression of Munc18 in dorsal root ganglion neurons did not affect CaV2.2 current amplitude or fast kinetics but siRNA-knockdown resulted in a negative shift in the steady state inactivation curve, an effect attributed to an indirect action via syntaxin 1. Recombinant Munc18 also co-precipitated strongly with the v-SNARE synaptotagmin but only weakly with other SNAREs. Thus, the calcium channel may serve as a surface membrane platform anchoring a Munc18-containing bridge to synaptotagmin and the synaptic vesicle.
Authors
Allen W. Chan
Toronto Western Research Institute
Rajesh Khanna
Toronto Western Research Institute
Qi Li
Toronto Western Research Institute
Elise F. Stanley
Toronto Western Research Institute
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.