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Regulation of calcium signaling by polycystin-2.

机译:多囊藻蛋白2对钙信号的调节。

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摘要

Autosomal dominant PKD (ADPKD) is a common lethal genetic disorder characterized by progressive development of fluid-filled cysts in the kidney and other target organs. ADPKD is caused by mutations in the PKD1 and PKD2 genes, encoding the transmembrane proteins polycystin-1 (PC1) and polycystin-2 (PC2), respectively. Although the function and putative interacting ligands of PC1 are largely unknown, recent evidence indicates that PC2 behaves as a TRP-type Ca(2+)-permeable nonselective cation channel. The PC2 channel is implicated in the transient increase in cytosolic Ca(2+) in renal epithelial cells and may be linked to the activation of subsequent signaling pathways. Recent studies also indicate that PC1 functionally interacts with PC2 such that the PC1-PC2 channel complex is an obligatory novel signaling pathway implicated in the transduction of environmental signals into cellular events. The present review purposely avoids issues of regulation of PC2 expression and trafficking and focuses instead onthe evidence for the TRP-type cation channel function of PC2. How its role as a cation channel may unmask mechanisms that trigger Ca(2+) transport and regulation is the focus of attention. PC2 channel function may be essential in renal cell function and kidney development. Nonrenal-targeted expression of PC2 and related proteins, including the cardiovascular system, also suggests previously unforeseeable roles in signal transduction.
机译:常染色体显性PKD(ADPKD)是常见的致死性遗传疾病,其特征是肾脏和其他靶器官中充满液体的囊肿逐渐发展。 ADPKD是由PKD1和PKD2基因的突变引起的,该基因分别编码跨膜蛋白polycystin-1(PC1)和polycystin-2(PC2)。虽然PC1的功能和假定的相互作用配体在很大程度上是未知的,但最近的证据表明PC2的行为就像是TRP型Ca(2+)渗透性非选择性阳离子通道。 PC2通道参与肾上皮细胞中的胞质Ca(2+)的瞬时增加,并且可能与后续信号通路的激活有关。最近的研究还表明,PC1在功能上与PC2相互作用,因此PC1-PC2通道复合物是强制性的新型信号传导途径,与环境信号转导到细胞事件有关。本综述的目的是避免调节PC2表达和运输的问题,而是着重于PC2的TRP型阳离子通道功能的证据。其作为阳离子通道的作用可能如何掩盖触发Ca(2+)传输和调节的机制,是关注的焦点。 PC2通道功能可能对肾细胞功能和肾脏发育至关重要。 PC2及其相关蛋白(包括心血管系统)的非肾脏靶向表达也暗示了信号转导中以前不可预见的作用。

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