Kinetic efficiency of endocytosis at mammalian CNS synapses requires synaptotagmin I.
At nerve terminals, synaptic vesicle components are retrieved from the cell surface and recycled for local reuse soon after exocytosis. The kinetics of this coupling is critical for the proper functioning of synapses during repetitive action potential firing, because deficiencies in this process lead to abnormal depletion of the releasable vesicle pool. Although the molecular basis of this coupling is poorly understood, numerous biochemical data point to a role for synaptotagmin I (SytI), an essential synaptic vesicle protein required for fast calcium-dependent exocytosis. Here, using synapto-pHluorin in an approach that allows the dissection of endocytosis and exocytosis into separate components during periods of stimulation, we examined exocytic-endocytic coupling in synapses from SytI knockout mice and their WT littermates. We show that endocytosis is significantly impaired in the absence of SytI with the relative rates of endocytosis compared with exocytosis reduced approximately 3-fold with respect to WT. Thus, in addition to regulating exocytosis, SytI also controls the kinetic efficiency of endocytosis at nerve terminals.
Nicholson-Tomishima
Karin
K
Department of Biochemistry, Weill Medical College of Cornell University, 1300 York Avenue, New York, NY 10021, USA.
Ryan
Timothy A
TA
D000818:Animals; D002135:Calcium-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D002540:Cerebral Cortex / Q000502:physiology; D004705:Endocytosis / Q000502:physiology*; D005089:Exocytosis / Q000502:physiology; D005260:Female; D007700:Kinetics; D008562:Membrane Glycoproteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008959:Models, Neurological; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D011247:Pregnancy; D017729:Presynaptic Terminals / Q000502:physiology; D013569:Synapses / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology; D050863:Synaptotagmin I; D050857:Synaptotagmins
D002135:Calcium-Binding Proteins; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D050863:Synaptotagmin I; C494311:Syt1 protein, mouse; D050857:Synaptotagmins