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News tips from the Journal of Neuroscience

1. Docking and Priming with Munc18
Attila Gulys-Kovcs, Heidi de Wit, Ira Milosevic, Olexiy Kochubey, Ruud Toonen, Jrgen Klingauf, Matthijs Verhage, and Jakob B. Srensen

This week, Gulys-Kovcs et al. unmask a dual role for Munc18 in docking and priming of vesicles in chromaffin cells. In vitro, Munc18 binds the "closed" state of syntaxin1 and thus occludes binding of the SNARE proteins SNAP-25 and synaptobrevin. However, Munc18 cannot be simply a negative regulator of exocytosis because vesicles fail to dock in its absence. To address this issue, the authors expressed mutant variants in chromaffin cells from Munc18 null mice and used uncaging of calcium to trigger release of primed vesicles. Expression of the NV mutation that prevents binding to closed syntaxin1 reduced vesicle docking. However, Munc18-1 NV rescued release, albeit to a lesser extent than wild type. Thus, Munc18 regulates a postdocking (priming) step by a mechanism that does not require binding to syntaxin1. In fact, the authors suggest that this second interaction either involves dissociation from syntaxin or a conformational change in the N-terminal domain of Munc18.


2. Pak1 and Neuronal Polarity
Tom Jacobs, Frdric Causeret, Yoshiaki V. Nishimura, Mami Terao, Adele Norman, Mikio Hoshino, and Margareta Nikolic

If you want to make axons, you will need some activated p21-activated kinase (Pak1), according to Jacobs et al. The authors found this CdC42 and cofilin effector in all neurites, but it was activated locally in nascent axons. In cultured hippocampal and cortical neurons, the levels of membrane-associated phosphorylated active) Pak1 peaked at the same time that neurons became polarized with distinct axons and dendrites, at ~ 2--4 d in Vitro (DIV). Total Pak1, in contrast, reached a plateau at 4 DIV and beyond. Total and activated Pak1 were evenly distributed among multiple neurites before polarization, but once a neurite
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Contact: Sara Harris
sharris@sfn.org
202-962-4000
Society for Neuroscience
7-Aug-2007


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