PKA-catalyzed phosphorylation of tomosyn and its implication in Ca2+-dependent exocytosis of neurotransmitter.
Neurotransmitter is released from nerve terminals by Ca2+-dependent exocytosis through many steps. SNARE proteins are key components at the priming and fusion steps, and the priming step is modulated by cAMP-dependent protein kinase (PKA), which causes synaptic plasticity. We show that the SNARE regulatory protein tomosyn is directly phosphorylated by PKA, which reduces its interaction with syntaxin-1 (a component of SNAREs) and enhances the formation of the SNARE complex. Electrophysiological studies using cultured superior cervical ganglion (SCG) neurons revealed that this enhanced formation of the SNARE complex by the PKA-catalyzed phosphorylation of tomosyn increased the fusion-competent readily releasable pool of synaptic vesicles and, thereby, enhanced neurotransmitter release. This mechanism was indeed involved in the facilitation of neurotransmitter release that was induced by a potent biological mediator, the pituitary adenylate cyclase-activating polypeptide, in SCG neurons. We describe the roles and modes of action of PKA and tomosyn in Ca2+-dependent neurotransmitter release.
Baba
Takeshi
T
Department of Molecular Biology and Biochemistry, Osaka University Graduate School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
Sakisaka
Toshiaki
T
Mochida
Sumiko
S
Takai
Yoshimi
Y
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002474:Cell-Free System / Q000378:metabolism; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases; D005089:Exocytosis / Q000502:physiology*; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010766:Phosphorylation; D010902:Pituitary Gland / Q000166:cytology / Q000201:enzymology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000378:metabolism*; D050683:R-SNARE Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D050600:SNARE Proteins / Q000378:metabolism; D017783:Superior Cervical Ganglion / Q000737:chemistry / Q000166:cytology / Q000378:metabolism; D013572:Synaptic Vesicles / Q000378:metabolism
D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D050683:R-SNARE Proteins; D050600:SNARE Proteins; C484769:Stxbp5 protein, rat; D017346:Protein Serine-Threonine Kinases; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases