ZO-1 determines adherens and gap junction localization at intercalated disks
ZO-1 determines adherens and gap junction localization at intercalated disks
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DOI：
10.1152/ajpheart.00999.2010
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发表时间：
2011-02-01
影响因子：
4.8
通讯作者：
Gourdie, Robert G.
中科院分区：
文献类型：
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作者：
Palatinus, Joseph A.;O'Quinn, Michael P.;Gourdie, Robert G.
Palatinus JA， O'Quinn MP, Barker RJ, Harris BS, Jourdan J, Gourdie RG。Zo-1决定嵌入盘的粘附物和间隙连接的定位。[J] .中国生物医学工程学报，2011,31(4):593 - 594。首次发表于2010年12月3日；doi: 10.1152 / ajpheart.00999.2010。心肌细胞插入盘（ICDs）机电连接空间秩序的破坏是许多心脏病状态的一个鲜为人知的特征。这里，体外和体内证据表明，zonula occludens-1 （ZO-1）调节icd间隙连接（GJs）和粘附连接（AJs）的组织。我们通过在大鼠心室肌细胞（vm）中表达一个显性阴性的ZO-1构建体（DN-ZO-1）来研究ZO-1对细胞-细胞连接定位的贡献。通过共定位和共免疫沉淀检测，DN-ZO-1在培养的新生儿vm中表达72 h，降低了ZO-1与n -钙粘蛋白的相互作用，促进了AJ和GJ蛋白的细胞质内化。体内成人vm中DN-ZO-1的表达也减少了n-钙粘蛋白与ZO-1的共定位，当使用Cx43中ZO-1结合配体的模拟物破坏连接蛋白-43 (Cx43)-ZO-1相互作用时，没有观察到这种现象。dn -ZO-1感染的vm在ICD周围表现出大的GJs，并且在面向磁盘内部的斑块边缘表现出局灶ZO-1浓度的丧失。此外，内部小gj和周围大gj的典型ICD模式也被打破。在出生后发育期间，vm中持续表达DN-ZO-1可降低icd相关的Cx43 GJs，并增加侧化和细胞质Cx43。我们得出结论，ZO-1调控GJ的定位是通过与n -钙粘蛋白多蛋白复合物的关联，这是ICD中AJs和GJ稳定定位的关键决定因素。
Palatinus JA, O'Quinn MP, Barker RJ, Harris BS, Jourdan J, Gourdie RG. Zo-1 determines adherens and gap junction localization at intercalated disks. Am J Physiol Heart Circ Physiol 300: H583-H594, 2011. First published December 3, 2010; doi: 10.1152/ajpheart.00999.2010.-The disruption of the spatial order of electromechanical junctions at myocyte-intercalated disks (ICDs) is a poorly understood characteristic of many cardiac disease states. Here, in vitro and in vivo evidence is provided that zonula occludens-1 (ZO-1) regulates the organization of gap junctions (GJs) and adherens junctions (AJs) at ICDs. We investigated the contribution of ZO-1 to cell-cell junction localization by expressing a dominant-negative ZO-1 construct (DN-ZO-1) in rat ventricular myocytes (VMs). The expression of DN-ZO-1 in cultured neonatal VMs for 72 h reduced the interaction of ZO-1 and N-cadherin, as assayed by colocalization and coimmunoprecipitation, prompting cytoplasmic internalization of AJ and GJ proteins. DN-ZO-1 expression in adult VMs in vivo also reduced N-cadherin colocalization with ZO-1, a phenomenon not observed when the connexin-43 (Cx43)-ZO-1 interaction was disrupted using a mimetic of the ZO-1-binding ligand from Cx43. DN-ZO-1-infected VMs demonstrated large GJs at the ICD periphery and showed a loss of focal ZO-1 concentrations along plaque edges facing the disk interior. Additionally, there was breakdown of the characteristic ICD pattern of small interior and large peripheral GJs. Continuous DN-ZO-1 expression in VMs over postnatal development reduced ICD-associated Cx43 GJs and increased lateralized and cytoplasmic Cx43. We conclude that ZO-1 regulation of GJ localization is via an association with the N-cadherin multiprotein complex and that this is a key determinant of stable localization of both AJs and GJs at the ICD.