PMID- 27143357
OWN - NLM
STAT- MEDLINE
DCOM- 20170508
LR  - 20210205
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 291
IP  - 30
DP  - 2016 Jul 22
TI  - Charged Residues at the First Transmembrane Region Contribute to the Voltage 
      Dependence of the Slow Gate of Connexins.
PG  - 15740-52
LID - 10.1074/jbc.M115.709402 [doi]
AB  - Connexins (Cxs) are a family of membrane-spanning proteins that form gap junction 
      channels and hemichannels. Connexin-based channels exhibit two distinct 
      voltage-dependent gating mechanisms termed slow and fast gating. Residues located 
      at the C terminus of the first transmembrane segment (TM-1) are important 
      structural components of the slow gate. Here, we determined the role of the 
      charged residues at the end of TM-1 in voltage sensing in Cx26, Cx46, and Cx50. 
      Conductance/voltage curves obtained from tail currents together with kinetics 
      analysis reveal that the fast and slow gates of Cx26 involves the movement of two 
      and four charges across the electric field, respectively. Primary sequence 
      alignment of different Cxs shows the presence of well conserved glutamate 
      residues in the C terminus of TM-1; only Cx26 contains a lysine in that position 
      (lysine 41). Neutralization of lysine 41 in Cx26 increases the voltage dependence 
      of the slow gate. Swapping of lysine 41 with glutamate 42 maintains the voltage 
      dependence. In Cx46, neutralization of negative charges or addition of a positive 
      charge in the Cx26 equivalent region reduced the slow gate voltage dependence. In 
      Cx50, the addition of a glutamate in the same region decreased the voltage 
      dependence, and the neutralization of a negative charge increased it. These 
      results indicate that the charges at the end of TM-1 are part of the slow gate 
      voltage sensor in Cxs. The fact that Cx42, which has no charge in this region, 
      still presents voltage-dependent slow gating suggests that charges still 
      unidentified also contribute to the slow gate voltage sensitivity.
CI  - (c) 2016 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Pinto, Bernardo I
AU  - Pinto BI
AD  - From the Centro Interdisciplinario de Neurociencias de Valparaiso, Universidad de 
      Valparaiso, Valparaiso 2360102 and.
FAU - Garcia, Isaac E
AU  - Garcia IE
AD  - From the Centro Interdisciplinario de Neurociencias de Valparaiso, Universidad de 
      Valparaiso, Valparaiso 2360102 and.
FAU - Pupo, Amaury
AU  - Pupo A
AD  - From the Centro Interdisciplinario de Neurociencias de Valparaiso, Universidad de 
      Valparaiso, Valparaiso 2360102 and.
FAU - Retamal, Mauricio A
AU  - Retamal MA
AD  - the Centro de Fisiologia Celular e Integrativa, Facultad de Medicina, Clinica 
      Alemana Universidad del Desarrollo, Santiago 7710162, Chile.
FAU - Martinez, Agustin D
AU  - Martinez AD
AD  - From the Centro Interdisciplinario de Neurociencias de Valparaiso, Universidad de 
      Valparaiso, Valparaiso 2360102 and.
FAU - Latorre, Ramon
AU  - Latorre R
AD  - From the Centro Interdisciplinario de Neurociencias de Valparaiso, Universidad de 
      Valparaiso, Valparaiso 2360102 and ramon.latorre@uv.cl.
FAU - Gonzalez, Carlos
AU  - Gonzalez C
AD  - From the Centro Interdisciplinario de Neurociencias de Valparaiso, Universidad de 
      Valparaiso, Valparaiso 2360102 and carlos.gonzalezl@uv.cl.
LA  - eng
SI  - PDB/2ZW3
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160503
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Avian Proteins)
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Avian Proteins/genetics/*metabolism
MH  - Chickens
MH  - Connexins/genetics/*metabolism
MH  - Humans
MH  - Ion Channel Gating/*physiology
MH  - Membrane Potentials/*physiology
MH  - Protein Domains
MH  - Rats
MH  - Xenopus laevis
PMC - PMC4957056
OTO - NOTNLM
OT  - biophysics
OT  - connexin
OT  - connexon (hemichannel)
OT  - electrophysiology
OT  - ion channel
OT  - kinetics
OT  - voltage dependency
EDAT- 2016/05/05 06:00
MHDA- 2017/05/10 06:00
PMCR- 2017/07/22
CRDT- 2016/05/05 06:00
PHST- 2015/12/10 00:00 [received]
PHST- 2016/05/05 06:00 [entrez]
PHST- 2016/05/05 06:00 [pubmed]
PHST- 2017/05/10 06:00 [medline]
PHST- 2017/07/22 00:00 [pmc-release]
AID - S0021-9258(20)39708-8 [pii]
AID - M115.709402 [pii]
AID - 10.1074/jbc.M115.709402 [doi]
PST - ppublish
SO  - J Biol Chem. 2016 Jul 22;291(30):15740-52. doi: 10.1074/jbc.M115.709402. Epub 
      2016 May 3.