A cytosolic splice variant of Cab45 interacts with Munc18b and impacts on amylase secretion by pancreatic acini

Patrick P.L. Lam, Kati Hyvärinen, Maria Kauppi, Laura Cosen-Binker, Saara Laitinen, Sirkka Keränen, Herbert Y. Gaisano (Corresponding Author), Vesa M. Olkkonen (Corresponding Author)

Research output: Contribution to journalArticleScientificpeer-review

25 Citations (Scopus)

Abstract

We identified in a yeast two-hybrid screen the EF-hand Ca2+-binding protein Cab45 as an interaction partner of Munc18b. Although the full-length Cab45 resides in Golgi lumen, we characterize a cytosolic splice variant, Cab45b, expressed in pancreatic acini. Cab45b is shown to bind 45Ca2+, and, of its three EF-hand motifs, EF-hand 2 is demonstrated to be crucial for the ion binding. Cab45b is shown to interact with Munc18b in an in vitro assay, and this interaction is enhanced in the presence of Ca2+. In this assay, Cab45b also binds the Munc18a isoform in a Ca2+-dependent manner. The endogenous Cab45b in rat acini coimmunoprecipitates with Munc18b, syntaxin 2, and syntaxin 3, soluble N-ethylmaleimide-sensitive factor attachment protein receptors with key roles in the Ca2+-triggered zymogen secretion. Furthermore, we show that Munc18b bound to syntaxin 3 recruits Cab45b onto the plasma membrane. Importantly, antibodies against Cab45b are shown to inhibit in a specific and dose-dependent manner the Ca2+-induced amylase release from streptolysin-O–permeabilized acini. The present study identifies Cab45b as a novel protein factor involved in the exocytosis of zymogens by pancreatic acini.
Original languageEnglish
Pages (from-to)2473-2480
JournalMolecular Biology of the Cell
Volume18
Issue number7
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

Keywords

  • pancreas
  • exocrine acinar cells
  • exocytosis
  • enzymes
  • enzyme production
  • genes
  • gene expression
  • SNARE
  • amylases

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    Lam, P. P. L., Hyvärinen, K., Kauppi, M., Cosen-Binker, L., Laitinen, S., Keränen, S., Gaisano, H. Y., & Olkkonen, V. M. (2007). A cytosolic splice variant of Cab45 interacts with Munc18b and impacts on amylase secretion by pancreatic acini. Molecular Biology of the Cell, 18(7), 2473-2480. https://doi.org/10.1091/mbc.E06-10-0950