PMID- 26152716
OWN - NLM
STAT- MEDLINE
DCOM- 20151117
LR  - 20210306
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 34
DP  - 2015 Aug 21
TI  - Rab11-dependent Recycling of the Human Ether-a-go-go-related Gene (hERG) Channel.
PG  - 21101-21113
LID - S0021-9258(20)42130-1 [pii]
LID - 10.1074/jbc.M115.636324 [doi]
AB  - The human ether-a-go-go-related gene (hERG) encodes the pore-forming subunit of 
      the rapidly activating delayed rectifier potassium channel (IKr). A reduction in 
      the hERG current causes long QT syndrome, which predisposes affected individuals 
      to ventricular arrhythmias and sudden death. We reported previously that hERG 
      channels in the plasma membrane undergo vigorous internalization under low K(+) 
      conditions. In the present study, we addressed whether hERG internalization 
      occurs under normal K(+) conditions and whether/how internalized channels are 
      recycled back to the plasma membrane. Using patch clamp, Western blot, and 
      confocal imaging analyses, we demonstrated that internalized hERG channels can 
      effectively recycle back to the plasma membrane. Low K(+)-enhanced hERG 
      internalization is accompanied by an increased rate of hERG recovery in the 
      plasma membrane upon reculture following proteinase K-mediated clearance of 
      cell-surface proteins. The increased recovery rate is not due to enhanced protein 
      synthesis, as hERG mRNA expression was not altered by low K(+) exposure, and the 
      increased recovery was observed in the presence of the protein biosynthesis 
      inhibitor cycloheximide. GTPase Rab11, but not Rab4, is involved in the recycling 
      of hERG channels. Interfering with Rab11 function not only delayed hERG recovery 
      in cells after exposure to low K(+) medium but also decreased hERG expression and 
      function in cells under normal culture conditions. We concluded that the 
      recycling pathway plays an important role in the homeostasis of plasma 
      membrane-bound hERG channels.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Chen, Jeffery
AU  - Chen J
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Guo, Jun
AU  - Guo J
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Yang, Tonghua
AU  - Yang T
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Li, Wentao
AU  - Li W
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Lamothe, Shawn M
AU  - Lamothe SM
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Kang, Yudi
AU  - Kang Y
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Szendrey, John A
AU  - Szendrey JA
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Zhang, Shetuan
AU  - Zhang S
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada. Electronic address: shetuan.zhang@queensu.ca.
LA  - eng
GR  - MOP 72911/Canadian Institutes of Health Research/Canada
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150707
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ERG1 Potassium Channel)
RN  - 0 (Ether-A-Go-Go Potassium Channels)
RN  - 0 (KCNH2 protein, human)
RN  - 0 (RNA, Messenger)
RN  - 98600C0908 (Cycloheximide)
RN  - EC 3.4.21.64 (Endopeptidase K)
RN  - EC 3.6.1.- (rab11 protein)
RN  - EC 3.6.5.2 (rab GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rab4 GTP-Binding Proteins)
RN  - RWP5GA015D (Potassium)
SB  - IM
MH  - Amino Acid Sequence
MH  - Cell Membrane/chemistry/drug effects/*metabolism
MH  - Cycloheximide/pharmacology
MH  - ERG1 Potassium Channel
MH  - Endopeptidase K/chemistry
MH  - Ether-A-Go-Go Potassium Channels/chemistry/genetics/*metabolism
MH  - Gene Expression
MH  - HEK293 Cells
MH  - Humans
MH  - Ion Transport
MH  - Molecular Sequence Data
MH  - Patch-Clamp Techniques
MH  - Potassium/*metabolism
MH  - Protein Transport
MH  - RNA, Messenger/genetics/*metabolism
MH  - rab GTP-Binding Proteins/genetics/*metabolism
MH  - rab4 GTP-Binding Proteins/genetics/*metabolism
PMC - PMC4543667
OTO - NOTNLM
OT  - cell-surface protein
OT  - electrophysiology
OT  - hERG
OT  - patch clamp
OT  - potassium channel
OT  - trafficking
EDAT- 2015/07/15 06:00
MHDA- 2015/11/18 06:00
PMCR- 2016/08/21
CRDT- 2015/07/09 06:00
PHST- 2015/01/02 00:00 [received]
PHST- 2015/07/09 06:00 [entrez]
PHST- 2015/07/15 06:00 [pubmed]
PHST- 2015/11/18 06:00 [medline]
PHST- 2016/08/21 00:00 [pmc-release]
AID - S0021-9258(20)42130-1 [pii]
AID - M115.636324 [pii]
AID - 10.1074/jbc.M115.636324 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Aug 21;290(34):21101-21113. doi: 10.1074/jbc.M115.636324. Epub 
      2015 Jul 7.