PMID- 23534605
OWN - NLM
STAT- MEDLINE
DCOM- 20130719
LR  - 20180816
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Linking)
VI  - 125
IP  - 5
DP  - 2013 Jun
TI  - Geranylgeranyltransferase I mediates BDNF-induced synaptogenesis.
PG  - 698-712
LID - 10.1111/jnc.12249 [doi]
AB  - Geranylgeranyltransferase I (GGT) is a prenyltransferase that mediates lipid 
      modification of Rho small GTPases, such as Rho, Rac, and Cdc42, which are 
      important for neuronal synaptogenesis. Although GGT is expressed in brain 
      extensively, the function of GGT in central nerves system is largely unknown so 
      far. We have previously demonstrated that GGT promotes the basal and neuronal 
      activity and brain-derived neurotrophic factor (BDNF)-induced dendritic 
      morphogenesis of cultured hippocampal neurons and cerebellar slices. This study 
      is to explore the function and mechanism of GGT in neuronal synaptogenesis. We 
      found that the protein level and activity of GGT gradually increased in rat 
      hippocampus from P7 to P28 and subcellular located at synapse of neurons. The 
      linear density of Synapsin 1 and post-synaptic density protein 95 increased by 
      over-expression of GGT beta, while reduced by inhibition or down-regulation of GGT. 
      In addition, GGT and its known substrate Rac was activated by BDNF, which 
      promotes synaptogenesis in cultured hippocampal neurons. Furthermore, 
      BDNF-induced synaptogenesis was eliminated by GGT inhibition or down-regulation, 
      as well as by non-prenylated Rac1 over-expression. Together, our data suggested 
      that GGT mediates BDNF-induced neuronal synaptogenesis through Rac1 activation.
CI  - (c) 2013 International Society for Neurochemistry.
FAU - Li, Zhengwei
AU  - Li Z
AD  - The Graduate School, Xuzhou Medical College, Xuzhou, Jiangsu, China.
FAU - Sun, Chengdong
AU  - Sun C
FAU - Zhang, Tao
AU  - Zhang T
FAU - Mo, Jianbing
AU  - Mo J
FAU - Shi, Qiong
AU  - Shi Q
FAU - Zhang, Xianfeng
AU  - Zhang X
FAU - Yuan, Maochun
AU  - Yuan M
FAU - Chen, Long
AU  - Chen L
FAU - Mao, Xueqiang
AU  - Mao X
FAU - Yu, Rutong
AU  - Yu R
FAU - Zhou, Xiuping
AU  - Zhou X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130419
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.5.- (Alkyl and Aryl Transferases)
RN  - EC 2.5.1.- (geranylgeranyltransferase type-I)
RN  - EC 3.6.5.2 (rac1 GTP-Binding Protein)
SB  - IM
MH  - Alkyl and Aryl Transferases/*physiology
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*pharmacology/physiology
MH  - Cells, Cultured
MH  - Hippocampus/drug effects/enzymology
MH  - Humans
MH  - Neurogenesis/drug effects/*physiology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Synapses/drug effects/*enzymology
MH  - rac1 GTP-Binding Protein/physiology
EDAT- 2013/03/29 06:00
MHDA- 2013/07/20 06:00
CRDT- 2013/03/29 06:00
PHST- 2012/07/22 00:00 [received]
PHST- 2013/03/21 00:00 [revised]
PHST- 2013/03/22 00:00 [accepted]
PHST- 2013/03/29 06:00 [entrez]
PHST- 2013/03/29 06:00 [pubmed]
PHST- 2013/07/20 06:00 [medline]
AID - 10.1111/jnc.12249 [doi]
PST - ppublish
SO  - J Neurochem. 2013 Jun;125(5):698-712. doi: 10.1111/jnc.12249. Epub 2013 Apr 19.