Acinar cell exocytosis requires spatiotemporal Ca2+ signals regulated through endoplasmic reticulum (ER) stores, Ca2+ATPases, and store-operated Ca2+ entry (SOCE). The secretory pathway Ca2+ATPase 2 (SPCA2) interacts with Orai1, which is involved in SOCE and store independent Ca2+ entry (SICE). However, in the pancreas, only a C-terminally truncated form of SPCA2 (termed SPAC2C) exists. The goal of this study was to determine if SPCA2C effects Ca2+ homeostasis in a similar fashion to the full-length SPCA2. Using epitope-tagged SPCA2C (SPCA2CFLAG) expressed in HEK293A cells and Fura2 imaging, cytosolic [Ca2+] was examined during SICE, SOCE and secretagogue-stimulated signaling. Exogenous SPCA2C expression increased resting cytosolic [Ca2+], Ca2+ release in response to carbachol, ER Ca2+ stores, and store-mediated and independent Ca2+ influx. Co-IP detected Orai1-SPCA2C interaction, which was altered by co-expression of STIM1. Importantly, SPCA2C's effects on store-mediated Ca2+ entry were independent of Orai1. These findings indicate SPCA2C influences Ca2+ homeostasis through multiple mechanisms, some of which are independent of Orai1, suggesting novel and possibly cell-specific Ca2+ regulation.

中文翻译：

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胰腺特异性形式的分泌途径钙ATPase 2调节参与钙稳态的多种途径。

腺泡细胞胞吐作用需要时空的Ca2 +信号，该信号通过内质网（ER）储存，Ca2 + ATPase和储存操作的Ca2 +进入（SOCE）来调节。分泌途径Ca2 + ATPase 2（SPCA2）与Orai1相互作用，后者参与SOCE并存储独立的Ca2 +进入（SICE）。但是，在胰腺中，仅存在C末端截短形式的SPCA2（称为SPAC2C）。这项研究的目的是确定SPCA2C是否以与全长SPCA2类似的方式影响Ca2 +稳态。使用在HEK293A细胞中表达的具有表位标签的SPCA2C（SPCA2CFLAG）和Fura2成像，在SICE，SOCE和促分泌素刺激的信号传导过程中检查了胞质[Ca2 +]。外源SPCA2C表达增加了静息胞质[Ca2 +]，Ca2 +的释放，以响应卡巴胆碱，ER Ca2 +存储以及存储介导的独立Ca2 +涌入。Co-IP检测到Orai1-SPCA2C相互作用，该相互作用被STIM1的共表达所改变。重要的是，SPCA2C对商店介导的Ca2 +进入的影响独立于Orai1。这些发现表明，SPCA2C通过多种机制影响Ca2 +稳态，其中某些机制与Orai1独立，这表明可能存在新型的细胞特异性Ca2 +调节。