Phosphorylation of synapsin I and MARCKS in nerve terminals is mediated by Ca2+ entry via an Aga-GI sensitive Ca2+ channel which is coupled to glutamate exocytosis.
Ca2+ entry is a prerequisite for both exocytosis and the phosphorylation of synapsin I and MARCKS proteins in mammalian cerebrocortical synaptosomes. The novel spider toxin Aga-GI completely blocks KCl-evoked glutamate exocytosis but only partially inhibits KCl-evoked cytoplasmic Ca2+ elevations, thus revealing at least two pathways for KCl-induced Ca2+ entry. Aga-GI completely attenuates KCl-induced phosphorylation of synapsin I and MARCKS proteins. We therefore conclude that both exocytosis and the phosphorylation of synapsin I and MARCKS proteins are specifically coupled to Ca2+ entry via a subset of voltage dependent Ca2+ channels at the nerve terminal which are sensitive to Aga-GI.
Coffey
E T
ET
Department of Biochemistry, University of Dundee, Scotland, UK.
Sihra
T S
TS
Nicholls
D G
DG
Pocock
J M
JM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D002540:Cerebral Cortex / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010766:Phosphorylation; D011189:Potassium Chloride / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013111:Spider Venoms / Q000494:pharmacology*; D016704:Synapsins / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
C077471:Aga-GI toxin; D015220:Calcium Channels; D047908:Intracellular Signaling Peptides and Proteins; C000619712:Marcks protein, rat; D008565:Membrane Proteins; D011506:Proteins; D013111:Spider Venoms; D016704:Synapsins; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D018698:Glutamic Acid; D011189:Potassium Chloride; D011493:Protein Kinase C; D002118:Calcium