title: Computer modeling of synapsin I binding to synaptic vesicles and F-actin: implications for regulation of neurotransmitter release.
abstract: Synapsin I is a neuron-specific phosphoprotein that binds to small synaptic vesicles and actin filaments in a phosphorylation-dependent fashion. It has been hypothesized that dephosphorylated synapsin I inhibits neurotransmitter release either by forming a cage around synaptic vesicles (cage model) or by anchoring them to the F-actin cytoskeleton of the nerve terminal (crosslinking model). Computer modeling was performed with the aim of testing the impact of phosphorylation on the molecular interactions of synapsin I within the nerve terminal. The results of the simulation experiments demonstrate that in the crosslinking model the phosphorylation of synapsin I causes a severalfold increase in the number of vesicles released from the cytoskeleton and that in the cage model the phosphorylation induces a 2-fold increase in the number of vesicles bearing one or more unsaturated synapsin I binding sites. These data are compatible with the view that the function of synapsin I in the short-term regulation of neurotransmitter release is to induce a phosphorylation-dependent transition of synaptic vesicles from a "reserve pool" to a readily "releasable pool" of vesicles.
authors.affiliation: Institute of Human Physiology, University of Modena, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Benfenati
authors.forename: F
authors.initials: F
authors.lastname: Valtorta
authors.forename: P
authors.initials: P
authors.lastname: Greengard
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D003198:Computer Simulation; D007700:Kinetics; D008433:Mathematics; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010750:Phosphoproteins / Q000378:metabolism*; D011485:Protein Binding; D016704:Synapsins; D013572:Synaptic Vesicles / Q000378:metabolism*
chemical_list: D000199:Actins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D010750:Phosphoproteins; D016704:Synapsins