The pancreas-specific form of secretory pathway calcium ATPase 2 regulates multiple pathways involved in calcium homeostasis

Authors

Melissa Fenech, Western UniversityFollow
McKenzie M Carter
Peter B Stathopulos, Western UniversityFollow
Christopher Pin, Western UniversityFollow

Document Type

Article

Publication Date

1-1-2020

Journal

Biochimica et Biophysica Acta: Molecular Cell Research

Volume

1867

Issue

1

First Page

118567

URL with Digital Object Identifier

https://doi.org/10.1016/j.bbamcr.2019.118567

Abstract

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 (SPCA2C^FLAG) 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.

Notes

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.

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