Expression and Function of Connexin 43 and Connexin 37 in the Murine Zona Glomerulosa

Gabriel Stolting, Nicole Hellmig, Hoang An Dinh, Marina Volkert, Ute I Scholl
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Abstract

The zona glomerulosa (ZG) synthesizes the mineralocorticoid aldosterone. The primary role of aldosterone is the maintenance of volume and electrolyte homeostasis. Aldosterone synthesis is primarily regulated via tightly controlled oscillations in intracellular calcium levels in response to stimulation. It has previously been shown that calcium oscillations are synchronized through mechanical linkage between adjacent ZG cells. In many other cell types, similar synchronization is rather dependent on gap junctions (GJ). The recent discovery of mutations in CADM1 was linked to impaired GJ function in the ZG. Based on published transcriptomics data, we re-examined the presence and functional impact of GJ in the ZG. We found evidence for the expression of connexin 43 and 37 in the ZG in microarray data, in-situ hybridization and immunohistology. Calcium oscillations in ZG rosettes showed some degree of synchronization as reported previously. Unspecific GJ inhibition only had a small impact on this synchronicity. However, no signs of connections between cytosols could be observed as indicated by the lack of fluorescence recovery after photobleaching. We conclude that, while connexin proteins are expressed in the ZG, functional GJ in the physiological ZG are rare and of little consequence for calcium signaling.
小鼠肾小球透明带中连接蛋白 43 和连接蛋白 37 的表达与功能
肾小球透明带(ZG)合成矿质类固醇醛固酮。醛固酮的主要作用是维持血容量和电解质平衡。醛固酮的合成主要是通过细胞内钙水平受严格控制的振荡来调节的。以前的研究表明,钙振荡是通过相邻 ZG 细胞之间的机械连接同步进行的。在许多其他类型的细胞中,类似的同步则依赖于间隙连接(GJ)。最近发现的 CADM1 突变与 ZG 中 GJ 功能受损有关。根据已发表的转录组学数据,我们重新研究了 GJ 在 ZG 中的存在及其功能影响。我们在芯片数据、原位杂交和免疫组织学中发现了 ZG 中连接蛋白 43 和 37 表达的证据。ZG 莲座丛中的钙振荡显示出一定程度的同步性,这与之前的报道相同。非特异性 GJ 抑制对这种同步性的影响很小。然而,光漂白后荧光没有恢复,这表明细胞溶胶之间没有连接的迹象。我们的结论是,虽然连接蛋白在 ZG 中表达,但生理 ZG 中的功能性 GJ 并不多见,而且对钙信号转导影响不大。
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