Cited 3 time in webofscience Cited 3 time in scopus

Loss of IQSEC3 Disrupts GABAergic Synapse Maintenance and Decreases Somatostatin Expression in the Hippocampus

Title
Loss of IQSEC3 Disrupts GABAergic Synapse Maintenance and Decreases Somatostatin Expression in the Hippocampus
Authors
Kim, SeungjoonKim, HyeonhoPark, DongseokKim, JinhuHong, JoohyeonKim, Jae SeongJung, HyejiKim, DongwookCheong, EunjiKo, JaewonUm, Ji Won
DGIST Authors
Ko, JaewonUm, Ji Won
Issue Date
2020-02
Citation
Cell Reports, 30(6), 1995-2005.e5
Type
Article
Article Type
Article
Keywords
DENTATE GRANULEGENE-EXPRESSIONEPILEPSYGEPHYRINMODELINTERNEURONSSEIZURESUSCEPTIBILITYTRANSMISSIONINHIBITION
ISSN
2211-1247
Abstract
Gephyrin interacts with various GABAergic synaptic proteins to organize GABAergic synapse development. Among the multitude of gephyrin-binding proteins is IQSEC3, a recently identified component at GABAergic synapses that acts through its ADP ribosylation factor-guanine nucleotide exchange factor (ARF-GEF) activity to orchestrate GABAergic synapse formation. Here, we show that IQSEC3 knockdown (KD) reduced GABAergic synaptic density in vivo, suggesting that IQSEC3 is required for GABAergic synapse maintenance in vivo. We further show that IQSEC3 KD in the dentate gyrus (DG) increases seizure susceptibility and triggers selective depletion of somatostatin (SST) peptides in the DG hilus in an ARF-GEP activity-dependent manner. Strikingly, selective introduction of SST into SST interneurons in DG-specific IQSEC3-KD mice reverses GABAergic synaptic deficits. Thus, our data suggest that IQSEC3 is required for linking gephyrin-GABAA receptor complexes with ARF-dependent pathways to prevent aberrant, runaway excitation and thereby contributes to the integrity of SST interneurons and proper GABAergic synapse maintenance. © 2020 The Author(s) In this study, Kim et al. investigate the effect of loss of function of IQSEC3, a gephyrin-binding GABAergic synapse-specific ARF-GEF, using hippocampal dentate gyrus (DG)-specific IQSEC3-knockdown (KD) mice. Strikingly, IQSEC3 KD causes a massive reduction of somatostatin (SST) expression. The restricted SST expression in SST+ interneurons reverses the pathological phenotypes. © 2020 The Author(s)
URI
http://hdl.handle.net/20.500.11750/11520
DOI
10.1016/j.celrep.2020.01.053
Publisher
Cell Press
Related Researcher
  • Author Ko, Jaewon Laboratory of Synapse Formation and Function
  • Research Interests Synapse Formation and Function; Neural Circuits; 뇌질환; animal model
Files:
Collection:
Department of Brain and Cognitive SciencesLaboratory of Synapse Formation and Function1. Journal Articles
Department of Brain and Cognitive SciencesSynapse Disorder Laboratory1. Journal Articles


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