PMID- 23703525
OWN - NLM
STAT- MEDLINE
DCOM- 20130917
LR  - 20211203
IS  - 1522-1563 (Electronic)
IS  - 0363-6143 (Print)
IS  - 0363-6143 (Linking)
VI  - 305
IP  - 2
DP  - 2013 Jul 15
TI  - Neuregulin-1/ErbB4 signaling regulates Kv4.2-mediated transient outward K+ 
      current through the Akt/mTOR pathway.
PG  - C197-206
LID - 10.1152/ajpcell.00041.2013 [doi]
AB  - Neuregulin-1 (NRG-1) is a member of a family of neurotrophic factors that is 
      required for the differentiation, migration, and development of neurons. NRG-1 
      signaling is thought to contribute to both neuronal development and the 
      neuropathology of schizophrenia, which is believed to be a neurodevelopmental 
      disorder. However, few studies have investigated the role of NRG-1 on 
      voltage-gated ion channels. In this study, we report that NRG-1 specifically 
      increases the density of transient outward K(+) currents (IA) in rat cerebellar 
      granule neurons (CGNs) in a time-dependent manner without modifying the 
      activation or inactivation properties of IA channels. The increase in IA density 
      is mediated by increased protein expression of Kv4.2, the main alpha-subunit of the 
      IA channel, most likely by upregulation of translation. The effect of NRG-1 on IA 
      density and Kv4.2 expression was only significant in immature neurons. 
      Mechanistically, both Akt and mammalian target of rapamycin (mTOR) signaling 
      pathways are required for the increased NRG-1-induced IA density and expression 
      of Kv4.2. Moreover, pharmacological blockade of the ErbB4 receptor reduced the 
      effect of NRG-1 on IA density and Kv4.2 induction. Our data reveal, for the first 
      time, that stimulation of ErbB4 signaling by NRG-1 upregulates the expression of 
      K(+) channel proteins via activation of the Akt/mTOR signaling pathway and plays 
      an important role in neuronal development and maturation. NRG1 does not acutely 
      change IA and delayed-rectifier outward (IK) of rat CGNs, suggesting that it may 
      not alter excitability of immature neurons by altering potassium channel 
      property.
FAU - Yao, Jin-Jing
AU  - Yao JJ
AD  - State Key Laboratory of Medical Neurobiology, School of Life Sciences and 
      Institutes of Brain Science, Fudan University, Shanghai, China.
FAU - Sun, Ji
AU  - Sun J
FAU - Zhao, Qian-Ru
AU  - Zhao QR
FAU - Wang, Chang-Ying
AU  - Wang CY
FAU - Mei, Yan-Ai
AU  - Mei YA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130522
PL  - United States
TA  - Am J Physiol Cell Physiol
JT  - American journal of physiology. Cell physiology
JID - 100901225
RN  - 0 (Neuregulin-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Shal Potassium Channels)
RN  - EC 2.7.10.1 (ErbB Receptors)
RN  - EC 2.7.10.1 (Erbb4 protein, rat)
RN  - EC 2.7.10.1 (Receptor, ErbB-4)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Animals
MH  - Cell Movement
MH  - ErbB Receptors/genetics/*metabolism
MH  - Gene Expression Regulation/physiology
MH  - Membrane Potentials
MH  - Neuregulin-1/genetics/*metabolism
MH  - Potassium/*metabolism
MH  - Proto-Oncogene Proteins c-akt/genetics/*metabolism
MH  - RNA, Messenger/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, ErbB-4
MH  - Shal Potassium Channels/genetics/*metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC3725632
OTO - NOTNLM
OT  - Akt/mTOR
OT  - CGNs
OT  - ErbB4
OT  - Ia
OT  - Kv4.2
OT  - neuregulin
EDAT- 2013/05/25 06:00
MHDA- 2013/09/18 06:00
PMCR- 2013/05/22
CRDT- 2013/05/25 06:00
PHST- 2013/05/25 06:00 [entrez]
PHST- 2013/05/25 06:00 [pubmed]
PHST- 2013/09/18 06:00 [medline]
PHST- 2013/05/22 00:00 [pmc-release]
AID - ajpcell.00041.2013 [pii]
AID - C-00041-2013 [pii]
AID - 10.1152/ajpcell.00041.2013 [doi]
PST - ppublish
SO  - Am J Physiol Cell Physiol. 2013 Jul 15;305(2):C197-206. doi: 
      10.1152/ajpcell.00041.2013. Epub 2013 May 22.