RCAN1 regulates vesicle recycling and quantal release kinetics via effects on calcineurin activity

Mark Zanin, Kimberly Mackenzie, Heshan Peiris, Melanie Pritchard, Damien Keating

    Research output: Contribution to journalArticle

    17 Citations (Scopus)

    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.

    Original languageEnglish
    Pages (from-to)290-299
    Number of pages10
    JournalJournal of Neurochemistry
    Volume124
    Issue number3
    DOIs
    Publication statusPublished - Feb 2013

    Keywords

    • amperometry
    • chromaffin cell
    • endocytosis
    • exocytosis
    • quantal release

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