Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Sci. STKE, 4 December 2001
Vol. 2001, Issue 111, p. tw448
[DOI: 10.1126/stke.2001.111.tw448]


Synaptic Vesicles Live! Synapsin Dynamics!

Calcium-stimulated secretion is a process with many well-characterized players, yet the exact mechanism by which calcium triggers the vesicle fusion process remains under investigation. Synapsins are a family of abundant synaptic phosphoproteins that dynamically associate with synaptic vesicles. Synapsins have sites for phosphorylation by multiple calcium/calmodulin kinases (CaMKs) and protein kinase A (PKA). Chi et al. used green fluorescent protein (GFP)-labeled synapsin Ia to monitor synapsin localization before, during, and after action potential stimulated secretion in hippocampal neurons. In addition, they monitored synaptic vesicle turnover using the fluorescent dye FM 4-64. Endogenous and GFP-synapsin disperses away from synaptic vesicles into the axon in response to action potential stimulation. Chi et al. were able to measure the rate of synapsin disperson and, using a series of mutants for the various CaMK sites, studied how phosphorylation controlled the kinetics of this process. Analysis of vesicle fusion and synapsin movement in cells expressing wild-type synapsin Ia and phosphorylation mutants of synapsin Ia showed a strong correlation between the rate of synapsin dispersion and the rate of vesicle fusion: The slower the synapsin dispersion, the slower the rate of vesicle turnover. This suggests that synapsin acts as a rate regulator, not an "on-off" switch for vesicle fusion. The analysis of the phosphorylation mutants expressed in wild-type or synapsin I- and II-deficient neurons led to two conclusions. First, the CaMK II phosphorylation sites (sites 2 and 3) appeared to regulate synapsin homo- and heterodimer formation. Second, the CaMK I and IV site (site 1), which is also a PKA phosphorylation site, appeared to regulate a direct interaction between synapsin and the vesicle that is independent of the synapsin-synapsin interaction. These real-time experiments provide "in synapse" verification for a model based on biochemical experiments for synapsin as an inhibitor of vesicle fusion under nonstimulated conditions and the release of synapsin upon calcium-dependent phosphorylation, allowing vesicle fusion to occur (see Murthy).

P. Chi, P. Greengard, T. A. Ryan, Synapsin dispersion and reclustering during synaptic activity. Nature Neurosci. 4, 1187-1193 (2001). [Online Journal]

V. N. Murthy, Spreading synapsins. Nature Neurosci. 4, 1155-1156 (2001). [Online Journal]

Citation: Live! Synapsin Dynamics! Sci. STKE 2001, tw448 (2001).

To Advertise     Find Products

Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882