![](https://d3ilqtpdwi981i.cloudfront.net/-CI9N7rBe7bPTf0pWKJsItmI6Wg=/425x550/smart/https://bepress-attached-resources.s3.amazonaws.com/uploads/17/c3/06/17c30689-ecfa-45b5-aadc-404871d09f70/thumbnail_860c9d40-b68b-43b7-8764-fe8e0a87e853.jpg)
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.
Available at: http://works.bepress.com/christopher-pin/5/
This article was published in Biochimica et Biophysica Acta: Molecular Cell Research and is available at https://doi.org/10.1016/j.bbamcr.2019.118567.