The gap junction cellular internet: connexin hemichannels enter the signalling limelight

被引:350
作者
Evans, W. Howard [1 ]
De Vuyst, Elke
Leybaert, Luc
机构
[1] Cardiff Univ, Sch Med, Dept Med Biochem & Immunol, Cardiff CF14 4XN, Wales
[2] Cardiff Univ, Sch Med, Wales Heart Res Inst, Cardiff CF14 4XN, Wales
[3] Univ Ghent, Dept Physiol & Pathophysiol, B-9000 Ghent, Belgium
关键词
apoptosis; ATP release; calcium channels; cell communication; Gap; 26; and; 27; mimetic peptides; rotigaptide;
D O I
10.1042/BJ20060175
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cxs (connexins), the protein subunits forming gap junction intercellular communication channels, are transported to the plasma membrane after oligomerizing into hexameric assemblies called connexin hemichannels (CxHcs) or connexons, which dock head-to-head with partner hexameric channels positioned on neighbouring cells. The double membrane channel or gap junction generated directly couples the cytoplasms of interacting cells and underpins the integration and co-ordination of cellular metabolism, signalling and functions, such as secretion or contraction in cell assemblies. In contrast, CxHcs prior to forming gap junctions provide a pathway for the release from cells of ATP, glutamate, NAD(+) and prostaglandin E-2, which act as paracrine messengers. ATP activates purinergic receptors on neighbouring cells and forms the basis of intercellular Ca2+ signal propagation, complementing that occuring more directly via gap junctions. CxHcs open in response to various types of external changes, including mechanical, shear, ionic and ischaemic stress. In addition, CxHcs are influenced by intracellular signals, such as membrane potential, phosphorylation and redox status, which translate external stresses to CxHc responses. Also, recent studies demonstrate that cytoplasmic Ca2+ changes in the physiological range act to trigger CxHc opening, indicating their involvement under normal non-pathological conditions. CxHcs not only respond to cytoplasmic Ca2+, but also determine cytoplasmic Ca2+, as they are large conductance channels, suggesting a prominent role in cellular Ca2+ homoeostasis and signalling. The functions of gap-junction channels and CxHcs have been difficult to separate, but synthetic peptides, that mimic short sequences in the Cx subunit are emerging as promising tools to determine the role of CxHcs in physiology and pathology.
引用
收藏
页码:1 / 14
页数:14
相关论文
共 203 条
[1]   Post-translational integration and oligomerization of connexin 26 in plasma membranes and evidence of formation of membrane pores: implications for the assembly of gap junctions [J].
Ahmad, S ;
Evans, WH .
BIOCHEMICAL JOURNAL, 2002, 365 (03) :693-699
[2]   Assembly of gap junction channels - Mechanism, effects of calmodulin antagonists and identification of connexin oligomerization determinants [J].
Ahmad, S ;
Martin, PEM ;
Evans, WH .
EUROPEAN JOURNAL OF BIOCHEMISTRY, 2001, 268 (16) :4544-4552
[3]   Molecular cloning and functional analysis of a novel Cx43 partner protein CIP150 [J].
Akiyama, M ;
Ishida, N ;
Ogawa, T ;
Yogo, K ;
Takeya, T .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 335 (04) :1264-1271
[4]   Evolution of gap junctions:: The missing link? [J].
Alexopoulos, H ;
Böttger, A ;
Fischer, S ;
Levin, A ;
Wolf, A ;
Fujisawa, T ;
Hayakawa, S ;
Gojobori, T ;
Davies, JA ;
David, CN ;
Bacon, JP .
CURRENT BIOLOGY, 2004, 14 (20) :R879-R880
[5]   Intercellular calcium signaling mediated by point-source burst release of ATP [J].
Arcuino, G ;
Lin, JHC ;
Takano, T ;
Liu, C ;
Jiang, L ;
Gao, Q ;
Kang, J ;
Nedergaard, M .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (15) :9840-9845
[6]   Conductive and kinetic properties of connexin45 hemichannels expressed in transfected HeLa cells [J].
Bader, P ;
Weingart, R .
JOURNAL OF MEMBRANE BIOLOGY, 2004, 199 (03) :143-154
[7]   Connexins are mechanosensitive [J].
Bao, L ;
Sachs, F ;
Dahl, G .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2004, 287 (05) :C1389-C1395
[8]   Pannexin membrane channels are mechanosensitive conduits for ATP [J].
Bao, L ;
Locovei, S ;
Dahl, G .
FEBS LETTERS, 2004, 572 (1-3) :65-68
[9]   Regulation of purified and reconstituted connexin 43 hemichannels by protein kinase C-mediated phosphorylation of serine 368 [J].
Bao, XY ;
Reuss, L ;
Altenberg, GA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (19) :20058-20066
[10]   Functional expression in Xenopus Oocytes of gap-junctional hemichannels formed by a cysteine-less connexin 43 [J].
Bao, XY ;
Chen, YY ;
Reuss, L ;
Altenberg, GA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2004, 279 (11) :9689-9692