Tang, Willcyn, Thevathasan, Jervis Vermal, Lin, Qingshu, Lim, Kim Buay, Kuroda, Keisuke, Kaibuchi, Kozo, Bilger, Marcel, Soong, Tuck Wah, Fivaz, Marc. 2016. Stimulation of Synaptic Vesicle Exocytosis by the Mental Disease Gene DISC1 is Mediated by N-Type Voltage-Gated Calcium Channels. Frontiers in Synaptic Neuroscience. 8

RIS

@ARTICLE{Tang2016,
title = {Stimulation of Synaptic Vesicle Exocytosis by the Mental Disease Gene DISC1 is Mediated by N-Type Voltage-Gated Calcium Channels},
author = {Willcyn Tang and Jervis Vermal Thevathasan and Qingshu Lin and Kim Buay Lim and Keisuke Kuroda and Kozo Kaibuchi and Marcel Bilger and Tuck Wah Soong and Marc Fivaz},
year = {2016},
doi = {http://dx.doi.org/10.3389/fnsyn.2016.00015},
volume = {8},
language = {EN},
journal = {Frontiers in Synaptic Neuroscience},
abstract = {Lesions and mutations of the DISC1 (Disrupted-in-schizophrenia-1) gene have been linked to major depression, schizophrenia, bipolar disorder and autism, but the influence of DISC1 on synaptic transmission remains poorly understood. Using two independent genetic approaches—RNAi and a DISC1 KO mouse—we examined the impact of DISC1 on the synaptic vesicle (SV) cycle by population imaging of the synaptic tracer vGpH in hippocampal neurons. DISC1 loss-of-function resulted in a marked decrease in SV exocytic rates during neuronal stimulation and was associated with reduced Ca2+ transients at nerve terminals. Impaired SV release was efficiently rescued by elevation of extracellular Ca2+, hinting at a link between DISC1 and voltage-gated Ca2+ channels. Accordingly, blockade of N-type Cav2.2 channels mimics and occludes the effect of DISC1 inactivation on SV exocytosis, and overexpression of DISC1 in a heterologous system increases Cav2.2 currents. Collectively, these results show that DISC1-dependent enhancement of SV exocytosis is mediated by Cav2.2 and point to aberrant glutamate release as a probable endophenotype of major psychiatric disorders.},
}