Phosphorylation of synapsin I by cAMP-dependent protein kinase controls synaptic vesicle dynamics in developing neurons.
In developing neurons, synaptic vesicles (SVs) undergo cycles of exo-endocytosis along isolated axons. However, it is currently unknown whether SV exocytosis is regulated before synaptogenesis. Here, we show that cAMP-dependent pathways affect SV distribution and recycling in the axonal growth cone and that these effects are mediated by the SV-associated phosphoprotein synapsin I. The presence of synapsin I on SVs is necessary for the correct localization of the vesicles in the central portion of the growth cone. Phosphorylation of synapsin I by cAMP-dependent protein kinase (protein kinase A) causes the dissociation of the protein from the SV membrane, allowing diffusion of the vesicles to the periphery of the growth cone and enhancing their rate of recycling. These results provide new clues as to the bases of the well known activity of synapsin I in synapse maturation and indicate that molecular mechanisms similar to those operating at mature nerve terminals are active in developing neurons to regulate the SV life cycle before synaptogenesis.
Bonanomi
Dario
D
Department of Neuroscience, San Raffaele Scientific Institute, Vita-Salute University, 20132 Milan, Italy.
Menegon
Andrea
A
Miccio
Annarita
A
Ferrari
Giuliana
G
Corradi
Anna
A
Kao
Hung-Teh
HT
Benfenati
Fabio
F
Valtorta
Flavia
F
D000818:Animals; D001369:Axons / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D020439:Growth Cones / Q000502:physiology / Q000648:ultrastructure; D006624:Hippocampus / Q000166:cytology* / Q000196:embryology*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism / Q000502:physiology*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016704:Synapsins / Q000378:metabolism*; D013572:Synaptic Vesicles / Q000502:physiology / Q000648:ultrastructure
D016704:Synapsins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases