MIST1 regulates the pancreatic acinar cell expression of Atp2c2, the gene encoding secretory pathway calcium ATPase 2

Victoria C. Garside, Agnes S. Kowalik, Charis L. Johnson, Daniel DiRenzo, Stephen F. Konieczny, Christopher L. Pin

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31 Citations (Scopus)

Abstract

MIST1 is a transcription factor expressed in pancreatic acinar cells and other serous exocrine cells. Mice harboring a targeted deletion of the Mist1 gene (Mist1-/-) exhibit alterations in acinar regulated exocytosis and aberrant Ca2+ signaling that are normally controlled by acinar cell Ca2+-ATPases. Previous studies indicated that total sarcoendoplasmic reticulum Ca2+-ATPases (SERCA) and plasma membrane Ca2+-ATPases (PMCA) remained unaffected in Mist1-/- acinar cultures. Therefore, we have assessed the expression of Atp2c2, the gene that encodes the secretory pathway Ca2+-ATPase 2 (SPCA2). We revealed a dramatic decrease in pancreatic expression of Atp2a2 mRNA and SPCA2 protein in Mist1-/- mice. Surprisingly, this analysis indicated that the acinar-specific Atp2c2 mRNA is a novel transcript, consisting of only the 3' end of the gene and the protein and localizes to the endoplasmic reticulum. Expression of SPCA2 was also lost in Mist1-/- secretory cells of the salivary glands and seminal vesicles, suggesting that Atp2c2 transcription is regulated by MIST1. Indeed, inducible MIST1 expression in Mist1-/- pancreatic acinar cells restored normal Atp2c2 expression, supporting a role for MIST1 in regulating the Atp2c2 gene. Based on these results, we have identified a new Atp2c2 transcript, the loss of which may be linked to the Mist1-/- phenotype.

Original languageEnglish
Pages (from-to)2859-2870
Number of pages12
JournalExperimental Cell Research
Volume316
Issue number17
DOIs
Publication statusPublished - Oct 2010
Externally publishedYes

Keywords

  • BHLH transcription factors
  • BHLHa15
  • Ca ATPases
  • Golgi apparatus
  • Pancreatic acinar cells
  • Regulated exocytosis

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