PMID- 31907062
OWN - NLM
STAT- MEDLINE
DCOM- 20210212
LR  - 20211204
IS  - 1756-6606 (Electronic)
IS  - 1756-6606 (Linking)
VI  - 13
IP  - 1
DP  - 2020 Jan 6
TI  - The small GTPase ARF6 regulates GABAergic synapse development.
PG  - 2
LID - 10.1186/s13041-019-0543-3 [doi]
LID - 2
AB  - ADP ribosylation factors (ARFs) are a family of small GTPases composed of six 
      members (ARF1-6) that control various cellular functions, including membrane 
      trafficking and actin cytoskeletal rearrangement, in eukaryotic cells. Among 
      them, ARF1 and ARF6 are the most studied in neurons, particularly at 
      glutamatergic synapses, but their roles at GABAergic synapses have not been 
      investigated. Here, we show that a subset of ARF6 protein is localized at 
      GABAergic synapses in cultured hippocampal neurons. In addition, we found that 
      knockdown (KD) of ARF6, but not ARF1, triggered a reduction in the number of 
      GABAergic synaptic puncta in mature cultured neurons in an ARF activity-dependent 
      manner. ARF6 KD also reduced GABAergic synaptic density in the mouse hippocampal 
      dentate gyrus (DG) region. Furthermore, ARF6 KD in the DG increased seizure 
      susceptibility in an induced epilepsy model. Viewed together, our results suggest 
      that modulating ARF6 and its regulators could be a therapeutic strategy against 
      brain pathologies involving hippocampal network dysfunction, such as epilepsy.
FAU - Kim, Hyeonho
AU  - Kim H
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), 333 Techno Jungangdae-Ro, Hyeonpoong-eup, Dalseong-gun, 
      Daegu, 42988, South Korea.
FAU - Jung, Hyeji
AU  - Jung H
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), 333 Techno Jungangdae-Ro, Hyeonpoong-eup, Dalseong-gun, 
      Daegu, 42988, South Korea.
FAU - Jung, Hyunsu
AU  - Jung H
AD  - Division of Life Sciences, Korea University, Seoul, 02841, South Korea.
AD  - Center for Functional Connectomics, Brain Science Institute, Korea Institute of 
      Science and Technology, Seoul, 02792, South Korea.
FAU - Kwon, Seok-Kyu
AU  - Kwon SK
AD  - Center for Functional Connectomics, Brain Science Institute, Korea Institute of 
      Science and Technology, Seoul, 02792, South Korea.
FAU - Ko, Jaewon
AU  - Ko J
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), 333 Techno Jungangdae-Ro, Hyeonpoong-eup, Dalseong-gun, 
      Daegu, 42988, South Korea.
FAU - Um, Ji Won
AU  - Um JW
AUID- ORCID: 0000-0002-9355-7726
AD  - Department of Brain and Cognitive Sciences, Daegu Gyeongbuk Institute of Science 
      and Technology (DGIST), 333 Techno Jungangdae-Ro, Hyeonpoong-eup, Dalseong-gun, 
      Daegu, 42988, South Korea. jiwonum@dgist.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20200106
PL  - England
TA  - Mol Brain
JT  - Molecular brain
JID - 101468876
RN  - 0 (ADP-Ribosylation Factor 6)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factor 1)
RN  - EC 3.6.5.2 (ADP-Ribosylation Factors)
RN  - EC 3.6.5.2 (ARF6 protein, human)
RN  - EC 3.6.5.2 (Arf6 protein, mouse)
RN  - EC 3.6.5.2 (Arf6 protein, rat)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - ADP-Ribosylation Factor 1/physiology
MH  - ADP-Ribosylation Factor 6
MH  - ADP-Ribosylation Factors/antagonists & inhibitors/genetics/*physiology
MH  - Animals
MH  - Cells, Cultured
MH  - GABAergic Neurons/*physiology/ultrastructure
MH  - Gene Knockdown Techniques
MH  - Genetic Vectors/genetics/therapeutic use
MH  - Hippocampus/cytology/embryology
MH  - Humans
MH  - Kainic Acid/toxicity
MH  - Male
MH  - Mice, Inbred C57BL
MH  - Point Mutation
MH  - RNA Interference
MH  - RNA, Small Interfering/genetics/pharmacology
MH  - Rats
MH  - Recombinant Proteins/metabolism
MH  - Seizures/chemically induced/genetics/physiopathology/prevention & control
MH  - Synapses/*metabolism
PMC - PMC6945580
OTO - NOTNLM
OT  - ARF
OT  - Epilepsy
OT  - GABA
OT  - Inhibitory synapse
COIS- The authors declare that they have no competing interests.
EDAT- 2020/01/08 06:00
MHDA- 2021/02/13 06:00
PMCR- 2020/01/06
CRDT- 2020/01/08 06:00
PHST- 2019/10/07 00:00 [received]
PHST- 2019/12/23 00:00 [accepted]
PHST- 2020/01/08 06:00 [entrez]
PHST- 2020/01/08 06:00 [pubmed]
PHST- 2021/02/13 06:00 [medline]
PHST- 2020/01/06 00:00 [pmc-release]
AID - 10.1186/s13041-019-0543-3 [pii]
AID - 543 [pii]
AID - 10.1186/s13041-019-0543-3 [doi]
PST - epublish
SO  - Mol Brain. 2020 Jan 6;13(1):2. doi: 10.1186/s13041-019-0543-3.