Synaptic vesicle mobilization is regulated by distinct synapsin I phosphorylation pathways at different frequencies.
During action potential firing, the rate of synapsin dissociation from synaptic vesicles and dispersion into axons controls the rate of vesicle availability for exocytosis at the plasma membrane. Here we show that synapsin Ia's dispersion rate tracks the synaptic vesicle pool turnover rate linearly over the range 5-20 Hz and that the molecular basis for this lies in regulation at both the calcium-calmodulin-dependent kinase (CaM kinase) and the mitogen-activated protein (MAP) kinase/calcineurin sites. Our results show that CaM kinase sites control vesicle mobilization at low stimulus frequency, while MAP kinase/calcineurin sites are critical at both lower and higher stimulus frequencies. Thus, multiple signaling pathways serve to allow synapsin's control of vesicle mobilization over different stimulus frequencies.
Chi
Ping
P
Department of Biochemistry, The Weill Medical College of Cornell University, 1300 York Avenue, New York, New York 10021, USA.
Greengard
Paul
P
Ryan
Timothy A
TA
D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D002478:Cells, Cultured; D004558:Electric Stimulation; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000166:cytology; D007202:Indicators and Reagents / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016297:Mutagenesis, Site-Directed / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D016704:Synapsins / Q000235:genetics / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000378:metabolism*
D007202:Indicators and Reagents; D008164:Luminescent Proteins; D016704:Synapsins; D049452:Green Fluorescent Proteins; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D019703:Calcineurin