RCAN1 regulates vesicle recycling and quantal release kinetics via effects on calcineurin activity
Date
2013
Authors
Zanin, M.P.
Mackenzie, K.D.
Peiris, H.
Pritchard, M.A.
Keating, D.J.
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Journal article
Citation
Journal of Neurochemistry, 2013; 124(3):290-299
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Abstract
We have previously shown that Regulator of Calcineurin 1 (RCAN1) regulates multiple stages of vesicle exocytosis. However, the mechanisms by which RCAN1 affects secretory vesicle exocytosis and quantal release kinetics remain unknown. Here, we use carbon fibre amperometry to detect exocytosis from chromaffin cells and identify these underlying mechanisms. We observe reduced exocytosis with repeated stimulations in chromaffin cells over-expressing RCAN1 (RCAN1ᵒˣ), but not in wild-type (WT) cells, indicating a negative effect of RCAN1 on vesicle recycling and endocytosis. Acute exposure to calcineurin inhibitors, cyclosporine A and FK-506, replicates this effect in WT cells but has no additional effect in RCAN1ᵒˣ cells. When we chronically expose WT cells to cyclosporine A and FK-506 we find that catecholamine release per vesicle and pre-spike foot (PSF) signal parameters are decreased, similar to that in RCAN1ᵒˣ cells. Inhibiting calcineurin activity in RCAN1ᵒˣ cells has no additional effect on the amount of catecholamine release per vesicle but further reduces PSF signal parameters. Although electron microscopy studies indicate these changes are not because of altered vesicle number or distribution in RCAN1ᵒˣ cells, the smaller vesicle and dense core size we observe in RCAN1ᵒˣ cells may underlie the reduced quantal release in these cells. Thus, our results indicate that RCAN1 most likely affects vesicle recycling and quantal release kinetics via the inhibition of calcineurin activity.
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Dissertation Note
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Description
Link to a related website: https://dspace.flinders.edu.au/xmlui/bitstream/2328/35198/1/Zanin_RCAN1_MS2013.pdf, Open Access via Unpaywall
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Copyright 2012 International Society for Neurochemistry