PMID- 25217644
OWN - NLM
STAT- MEDLINE
DCOM- 20141231
LR  - 20231213
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 289
IP  - 44
DP  - 2014 Oct 31
TI  - Structural determinants and proliferative consequences of connexin 37 hemichannel 
      function in insulinoma cells.
PG  - 30379-30386
LID - S0021-9258(20)37248-3 [pii]
LID - 10.1074/jbc.M114.583054 [doi]
AB  - Connexin (Cx) 37 suppresses vascular and cancer cell proliferation. The C 
      terminus and a channel able to function are necessary, and neither by itself is 
      sufficient, for Cx37 to mediate growth suppression. Cx37 supports transmembrane 
      and intercellular signaling by forming functional hemichannels (HCs) and gap 
      junction channels (GJCs), respectively. Here we determined whether Cx37 with HC, 
      but not GJC, functionality would suppress proliferation of rat insulinoma (Rin) 
      cells comparably to wild-type Cx37 (Cx37-WT). We mutated extracellular loop 
      residues hypothesized to compromise HC docking but not HC function (six cysteines 
      mutated to alanine, C54A,C61A,C65A, C187A,C192A,C198A (designated as C6A); N55I; 
      and Q58L). All three mutants trafficked to the plasma membrane and formed protein 
      plaques comparably to Cx37-WT. None of the mutants formed functional GJCs, and 
      Cx37-C6A did not form functional HCs. Cx37-N55I and -Q58L formed HCs with 
      behavior and permeation properties similar to Cx37-WT (especially Q58L), but none 
      of the mutants suppressed Rin cell proliferation. The data indicate that 
      determinants of Cx37 HC function differ from other Cxs and that HC functions with 
      associated HC-supported protein-protein interactions are not sufficient for Cx37 
      to suppress Rin cell proliferation. Together with previously published data, 
      these results suggest that Cx37 suppresses Rin cell proliferation only when in a 
      specific conformation achieved by interaction of the C terminus with a Cx37 
      pore-forming domain able to open as a GJC.
CI  - (c) 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Good, Miranda E
AU  - Good ME
AD  - Department of Physiology, University of Arizona, Tucson, Arizona 85724-5051.
FAU - Ek-Vitorin, Jose F
AU  - Ek-Vitorin JF
AD  - Department of Physiology, University of Arizona, Tucson, Arizona 85724-5051.
FAU - Burt, Janis M
AU  - Burt JM
AD  - Department of Physiology, University of Arizona, Tucson, Arizona 85724-5051. 
      Electronic address: jburt@u.arizona.edu.
LA  - eng
GR  - F32 HL131399/HL/NHLBI NIH HHS/United States
GR  - R01 HL058732/HL/NHLBI NIH HHS/United States
GR  - T32 HL007249/HL/NHLBI NIH HHS/United States
GR  - T32HL007249/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140912
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Connexins)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Cell Line, Tumor
MH  - *Cell Proliferation
MH  - Connexins/*physiology
MH  - Gap Junctions/metabolism
MH  - Insulinoma
MH  - Ion Channel Gating
MH  - Membrane Potentials
MH  - Mutation, Missense
MH  - Protein Transport
MH  - Rats
MH  - Signal Transduction
MH  - Gap Junction alpha-4 Protein
PMC - PMC4215222
OTO - NOTNLM
OT  - Arterial Endothelium
OT  - Cell Cycle Control
OT  - Cell-Cell Interaction
OT  - Connexin
OT  - Gap Junction
OT  - Hemichannel
OT  - Intercellular Communication
OT  - Proliferation
OT  - Protein Targeting
EDAT- 2014/09/14 06:00
MHDA- 2015/01/01 06:00
PMCR- 2015/10/31
CRDT- 2014/09/14 06:00
PHST- 2014/09/14 06:00 [entrez]
PHST- 2014/09/14 06:00 [pubmed]
PHST- 2015/01/01 06:00 [medline]
PHST- 2015/10/31 00:00 [pmc-release]
AID - S0021-9258(20)37248-3 [pii]
AID - M114.583054 [pii]
AID - 10.1074/jbc.M114.583054 [doi]
PST - ppublish
SO  - J Biol Chem. 2014 Oct 31;289(44):30379-30386. doi: 10.1074/jbc.M114.583054. Epub 
      2014 Sep 12.