ELKS2alpha/CAST deletion selectively increases neurotransmitter release at inhibitory synapses.
The presynaptic active zone is composed of a protein network that contains ELKS2alpha (a.k.a. CAST) as a central component. Here we demonstrate that in mice, deletion of ELKS2alpha caused a large increase in inhibitory, but not excitatory, neurotransmitter release, and potentiated the size, but not the properties, of the readily-releasable pool of vesicles at inhibitory synapses. Quantitative electron microscopy revealed that the ELKS2alpha deletion did not change the number of docked vesicles or other ultrastructural parameters of synapses, except for a small decrease in synaptic vesicle numbers. The ELKS2alpha deletion did, however, alter the excitatory/inhibitory balance and exploratory behaviors, possibly as a result of the increased synaptic inhibition. Thus, as opposed to previous studies indicating that ELKS2alpha is essential for mediating neurotransmitter release, our results suggest that ELKS2alpha normally restricts release and limits the size of the readily-releasable pool of synaptic vesicles at the active zone of inhibitory synapses.
Kaeser
Pascal S
PS
Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Palo Alto, CA 94304-5543, USA.
Deng
Lunbin
L
Chávez
Andrés E
AE
Liu
Xinran
X
Castillo
Pablo E
PE
Südhof
Thomas C
TC
D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000502:physiology; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics; D002478:Cells, Cultured; D004558:Electric Stimulation / Q000379:methods; D019204:GTP-Binding Proteins / Q000378:metabolism; D017353:Gene Deletion; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000502:physiology; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000235:genetics* / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008959:Models, Neurological; D009068:Movement / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000172:deficiency* / Q000235:genetics; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism*; D018408:Patch-Clamp Techniques / Q000379:methods; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D013574:Synaptosomes / Q000378:metabolism / Q000648:ultrastructure; D020691:rab GTP-Binding Proteins
D002352:Carrier Proteins; C486769:Erc1 protein, mouse; D009419:Nerve Tissue Proteins; D018377:Neurotransmitter Agents; D020033:Protein Isoforms; C491490:Rims1 protein, mouse; D049452:Green Fluorescent Proteins; D019204:GTP-Binding Proteins; D020691:rab GTP-Binding Proteins; D002118:Calcium