Increased association of ZO-1 with connexin43 during remodeling of cardiac gap junctions

被引:161
作者
Barker, RJ
Price, RL
Gourdie, RG
机构
[1] Med Univ S Carolina, Dept Cell Biol, Charleston, SC 29425 USA
[2] Med Univ S Carolina, Dept Anat, Charleston, SC 29425 USA
[3] Univ S Carolina, Sch Med, Dept Dev Biol & Anat, Columbia, SC 29208 USA
关键词
heart; gap junction; connexin; PDZ; ZO-1;
D O I
10.1161/hh0302.104471
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The intercellular geometry of connexin43 (Cx43) gap junctional coupling is key to coordinated spread of electrical activation through the ventricle of the mammalian heart. A progressive redistribution of electrical and mechanical junctions into intercalated discs occurs during postnatal development. Breakdown of disc-localized pattern in the adult heart, to recapitulate immature distributions, is thought to be key to the genesis of conduction disturbance and arrhythmia. Recently, ZO-1 (a PDZ-MAGUK protein), has been suggested to have a role in generating coupling geometries between myocytes. We therefore investigated the codistribution of ZO-1 with Cx43 and N-cadherin in the adult rat ventricle using quantitative immunoconfocal and immunoelectron microscopy. These analyses indicated that, whereas ZO-1 and Cx43 codistribute within discs, only low to moderate point-by-point colocalization of Cx43 and ZO-1 is found within these domains compared with the relatively high level of colocalization between N-cadherin and ZO-1. By contrast, levels of association between Cx43 and ZO-1 increased rapidly and significantly (P<0.001) after partial or complete enzymatic dissociation of myocytes from intact ventricle-a treatment known to induce gap junction endocytosis. Coimmunoprecipitation using Cx43- and ZO-1-specific antibodies confirmed that significantly (P<0.03) increased ZO-1 is precipitated relative to Cx43 in freshly dissociated myocytes as compared with intact ventricle. On immunoblots, decreases in Cx43 relative mobility, consistent with increased phosphorylation, were observed following myocyte dissociation. The increased ZO-1-Cx43 association that occurs after remodeling of myocyte intercellular contacts indicates the possibility of unanticipated roles for ZO-1 in gap junction turnover during cardiac development and disease processes.
引用
收藏
页码:317 / 324
页数:8
相关论文
共 43 条
[11]   Conduction slowing and sudden arrhythmic death in mice with cardiac-restricted inactivation of connexin43 [J].
Gutstein, DE ;
Morley, GE ;
Tamaddon, H ;
Vaidya, D ;
Schneider, MD ;
Chen, J ;
Chien, KR ;
Stuhlmann, H ;
Fishman, GI .
CIRCULATION RESEARCH, 2001, 88 (03) :333-339
[12]   CALCIUM TOLERANT VENTRICULAR MYOCYTES PREPARED BY PRE-INCUBATION IN A KB MEDIUM [J].
ISENBERG, G ;
KLOCKNER, U .
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY, 1982, 395 (01) :6-18
[13]   Involvement of ZO-1 in cadherin-based cell adhesion through its direct binding to or catenin and actin filaments [J].
Itoh, M ;
Nagafuchi, A ;
Moroi, S ;
Tsukita, S .
JOURNAL OF CELL BIOLOGY, 1997, 138 (01) :181-192
[14]   A 220-KD UNDERCOAT-CONSTITUTIVE PROTEIN - ITS SPECIFIC LOCALIZATION AT CADHERIN-BASED CELL CELL-ADHESION SITES [J].
ITOH, M ;
YONEMURA, S ;
NAGAFUCHI, A ;
TSUKITA, S ;
TSUKITA, S .
JOURNAL OF CELL BIOLOGY, 1991, 115 (05) :1449-1462
[15]  
Laird DW, 2001, METH MOL B, V154, P135
[17]   Phosphorylation of connexin43 on serine368 by protein kinase C regulates gap junctional communication [J].
Lampe, PD ;
TenBroek, EM ;
Burt, JM ;
Kurata, WE ;
Johnson, RG ;
Lau, AF .
JOURNAL OF CELL BIOLOGY, 2000, 149 (07) :1503-1512
[18]   BIOLOGICAL IMPLICATIONS OF GAP JUNCTION STRUCTURE, DISTRIBUTION AND COMPOSITION - A REVIEW [J].
LARSEN, WJ .
TISSUE & CELL, 1983, 15 (05) :645-671
[19]   EVIDENCE FOR THE PARTICIPATION OF ACTIN MICROFILAMENTS AND BRISTLE COATS IN THE INTERNALIZATION OF GAP JUNCTION MEMBRANE [J].
LARSEN, WJ ;
TUNG, HN ;
MURRAY, SA ;
SWENSON, CA .
JOURNAL OF CELL BIOLOGY, 1979, 83 (03) :576-587