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

Mol Biol Cell. 2007 Jul;18(7):2473-80. doi: 10.1091/mbc.e06-10-0950. Epub 2007 Apr 18.


We identified in a yeast two-hybrid screen the EF-hand Ca(2+)-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 (45)Ca(2+), 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 Ca(2+). In this assay, Cab45b also binds the Munc18a isoform in a Ca(2+)-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 Ca(2+)-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 Ca(2+)-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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alternative Splicing / drug effects
  • Alternative Splicing / genetics*
  • Amylases / metabolism*
  • Animals
  • Antibodies
  • Bacterial Proteins / pharmacology
  • CHO Cells
  • COS Cells
  • Calcium / metabolism
  • Calcium-Binding Proteins / chemistry
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Cell Membrane Permeability / drug effects
  • Chlorocebus aethiops
  • Cricetinae
  • Cricetulus
  • Cytosol / drug effects
  • Cytosol / metabolism*
  • Dogs
  • EF Hand Motifs
  • Gene Expression Profiling
  • Glycoproteins / chemistry
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Humans
  • Munc18 Proteins / metabolism*
  • Pancreas, Exocrine / drug effects
  • Pancreas, Exocrine / enzymology*
  • Pancreas, Exocrine / metabolism
  • Protein Binding / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Streptolysins / pharmacology


  • Antibodies
  • Bacterial Proteins
  • Calcium-Binding Proteins
  • Glycoproteins
  • Munc18 Proteins
  • RNA, Messenger
  • Streptolysins
  • streptolysin O
  • SDF4 protein, human
  • Amylases
  • Calcium