CAPS-1 and CAPS-2 are essential synaptic vesicle priming proteins.
Before transmitter-filled synaptic vesicles can fuse with the plasma membrane upon stimulation they have to be primed to fusion competence. The regulation of this priming process controls the strength and plasticity of synaptic transmission between neurons, which in turn determines many complex brain functions. We show that CAPS-1 and CAPS-2 are essential components of the synaptic vesicle priming machinery. CAPS-deficient neurons contain no or very few fusion competent synaptic vesicles, which causes a selective impairment of fast phasic transmitter release. Increases in the intracellular Ca(2+) levels can transiently revert this defect. Our findings demonstrate that CAPS proteins generate and maintain a highly fusion competent synaptic vesicle pool that supports phasic Ca(2+) triggered release of transmitters.
Jockusch
Wolf J
WJ
Max Planck Institute of Experimental Medicine, Department of Molecular Neurobiology, Hermann-Rein-Str. 3, D-37075 Göttingen, Germany.
Speidel
Dina
D
Sigler
Albrecht
A
Sørensen
Jakob B
JB
Varoqueaux
Frederique
F
Rhee
Jeong-Seop
JS
Brose
Nils
N
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D008561:Membrane Fusion / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D018377:Neurotransmitter Agents / Q000378:metabolism; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000737:chemistry / Q000378:metabolism / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D013572:Synaptic Vesicles / Q000378:metabolism*
C480975:CAPS2 protein, mouse; C510820:Cadps protein, mouse; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; C503321:Unc13a protein, mouse; D002118:Calcium