Local sharing as a predominant determinant of synaptic matrix molecular dynamics.
Recent studies suggest that central nervous system synapses can persist for weeks, months, perhaps lifetimes, yet little is known as to how synapses maintain their structural and functional characteristics for so long. As a step toward a better understanding of synaptic maintenance we examined the loss, redistribution, reincorporation, and replenishment dynamics of Synapsin I and ProSAP2/Shank3, prominent presynaptic and postsynaptic matrix molecules, respectively. Fluorescence recovery after photobleaching and photoactivation experiments revealed that both molecules are continuously lost from, redistributed among, and reincorporated into synaptic structures at time-scales of minutes to hours. Exchange rates were not affected by inhibiting protein synthesis or proteasome-mediated protein degradation, were accelerated by stimulation, and greatly exceeded rates of replenishment from somatic sources. These findings indicate that the dynamics of key synaptic matrix molecules may be dominated by local protein exchange and redistribution, whereas protein synthesis and degradation serve to maintain and regulate the sizes of local, shared pools of these proteins.
Tsuriel
Shlomo
S
The Rappaport Family Institute for Research in the Medical Sciences, Technion Faculty of Medicine, Haifa, Israel.
Geva
Ran
R
Zamorano
Pedro
P
Dresbach
Thomas
T
Boeckers
Tobias
T
Gundelfinger
Eckart D
ED
Garner
Craig C
CC
Ziv
Noam E
NE
D000818:Animals; D000831:Animals, Newborn; D001692:Biological Transport; D002352:Carrier Proteins / Q000378:metabolism; D002450:Cell Communication / Q000502:physiology; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003713:Dendritic Cells / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology; D009419:Nerve Tissue Proteins; D009473:Neuronal Plasticity / Q000502:physiology; D017729:Presynaptic Terminals / Q000737:chemistry; D011489:Protein Denaturation / Q000187:drug effects; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D021381:Protein Transport; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*; D016704:Synapsins / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D014018:Tissue Distribution
D002352:Carrier Proteins; D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D009419:Nerve Tissue Proteins; D011500:Protein Synthesis Inhibitors; C492357:SHANK3 protein, human; D016704:Synapsins; D049452:Green Fluorescent Proteins; D003513:Cycloheximide; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde