Franzini-Armstrong Clara, Protasi Feliciano, Tijskens Pierre
Department of Cell and Developmental Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Ann N Y Acad Sci. 2005 Jun;1047:76-85. doi: 10.1196/annals.1341.007.
Calcium release units (CRUs) are constituted of specialized junctional domains of the sarcoplasmic reticulum (jSR) that bear calcium release channels, also called ryanodine receptors (RyRs). In cardiac muscle, CRUs come in three subtypes that differ in geometry, but have common molecular components. Peripheral couplings are formed by a junction of the jSR with the plasmalemma; dyads occur where the jSR is associated with transverse (T)-tubules; corbular SR is a jSR domain that is located within the cells and bears RyRs but does not associate with either plasmalemma or T-tubules. Using transmission electron microscopy, this study followed the formation of CRUs and their accrual of four components: the L-type channel dihydropyridine receptors (DHPRs) of plasmalemma/T-tubules; the RyRs of jSR; triadin (Tr) and junctin (JnC), two homologous components of the jSR membrane; and calsequestrin (CSQ), the internal calcium binding proteins. During differentiation, peripheral couplings are formed first and the others follow. RyRs and DHPRs are targeted to subdomains of the CRUs that face each other and are acquired in a concerted manner. Overexpressions of either junction (JnC or Tr) and of CSQ, singly or in conjunction, shed light on the specific role of JnC in the structural development, organization, and maintenance of jSR cisternae and on the independent synthetic pathways and targeting of JnC and CSQ. In addition, the structural cues provided by the overexpression models allow us to define sequential steps in the synthetic pathway for JnC and CSQ and their targeting to the CRUs of differentiating myocardium.
钙释放单元（CRUs）由肌浆网（jSR）的特化连接结构域构成，这些结构域带有钙释放通道，也称为兰尼碱受体（RyRs）。在心肌中，CRUs有三种亚型，它们在几何结构上有所不同，但具有共同的分子成分。外周偶联是由jSR与质膜的连接形成的；二联体出现在jSR与横管（T管）相关联的部位；泡状肌浆网是位于细胞内的jSR结构域，带有RyRs，但不与质膜或T管相关联。本研究利用透射电子显微镜观察了CRUs的形成及其四种成分的积累：质膜/T管的L型通道二氢吡啶受体（DHPRs）；jSR的RyRs；三联蛋白（Tr）和连接蛋白（JnC），jSR膜的两个同源成分；以及肌集钙蛋白（CSQ），一种内部钙结合蛋白。在分化过程中，外周偶联首先形成，其他随后形成。RyRs和DHPRs靶向于CRUs中彼此相对的亚结构域，并以协同方式获得。单独或联合过表达连接蛋白（JnC或Tr）和CSQ，揭示了JnC在jSR池的结构发育、组织和维持中的特定作用，以及JnC和CSQ的独立合成途径和靶向。此外，过表达模型提供的结构线索使我们能够确定JnC和CSQ合成途径中的连续步骤及其向分化心肌CRUs的靶向。
