@article{8c0eccf0fb7111de825d000ea68e967b,
title = "Regulation of releasable vesicle pool sizes by protein kinase A-dependent phosphorylation of SNAP-25",
abstract = "Protein kinase A (PKA) is a key regulator of neurosecretion, but the molecular targets remain elusive. We combined pharmacological manipulations of kinase and phosphatase activities with mutational studies on the exocytotic machinery driving fusion of catecholamine-containing vesicles from chromaffin cells. We found that constitutive PKA activity was necessary to maintain a large number of vesicles in the release-ready, so-called primed, state, whereas calcineurin (protein phosphatase 2B) activity antagonized this effect. Overexpression of the SNARE protein SNAP-25a mutated in a PKA phosphorylation site (Thr-138) eliminated the effect of PKA inhibitors on the vesicle priming process. Another, unidentified, PKA target regulated the relative size of two different primed vesicle pools that are distinguished by their release kinetics. Overexpression of the SNAP-25b isoform increased the size of both primed vesicle pools by a factor of two, and mutations in the conserved Thr-138 site had similar effects as in the a isoform.",
author = "G{\'a}bor Nagy and Kerstin Reim and Ulf Matti and Nils Brose and Thomas Binz and Jens Rettig and Erwin Neher and S{\o}rensen, {Jakob B}",
note = "Keywords: Alanine; Animals; Blotting, Western; Calcineurin; Calcium; Carbazoles; Carrier Proteins; Catecholamines; Cattle; Cells, Cultured; Chromaffin Cells; Cyclic AMP; Cyclic AMP-Dependent Protein Kinases; Drug Interactions; Embryo, Mammalian; Enzyme Inhibitors; Exocytosis; Forskolin; Humans; Indoles; Intracellular Signaling Peptides and Proteins; Kidney; Membrane Potentials; Membrane Proteins; Models, Biological; Mutation; Nerve Tissue Proteins; Patch-Clamp Techniques; Peptide Fragments; Phosphorylation; Photolysis; Pyrethrins; Pyrroles; Secretory Vesicles; Synaptosomal-Associated Protein 25; Threonine; Time Factors; Transfection",
year = "2004",
language = "English",
volume = "41",
pages = "417--29",
journal = "Neuron",
issn = "0896-6273",
publisher = "Cell Press",
number = "3",
}