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BRAG about (s)lots
Joshua C Brown1,2, Johannes W Hell3, Nashaat Z Gerges4
1Division of Depression and Anxiety Disorders, Brain Stimulation Mechanisms Laboratory, McLean Hospital, Belmont, MA, USA.
Abstract:
Mutations in IQSEC2/BRAG1 cause intellectual dysfunction by impairing ARF-GEF activity and long-term depression. In this issue, Bai et al. (https://doi.org/10.1083/jcb.202307117) discover how constitutive ARF-GEF activity is regulated by a closed conformation which opens in the presence of Ca2+. Two known pathogenic mutations cause "leaky" autoinhibition with reduced synaptic dynamic range and impaired cognitive performance.
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