RGD Reference Report - A cytosolic splice variant of Cab45 interacts with Munc18b and impacts on amylase secretion by pancreatic acini. - Rat Genome Database

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

Authors: Lam, PP  Hyvarinen, K  Kauppi, M  Cosen-Binker, L  Laitinen, S  Keranen, S  Gaisano, HY  Olkkonen, VM 
Citation: Lam PP, etal., Mol Biol Cell. 2007 Jul;18(7):2473-80. Epub 2007 Apr 18.
RGD ID: 2312426
Pubmed: (View Article at PubMed) PMID:17442889
DOI: Full-text: DOI:10.1091/mbc.E06-10-0950

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.

Annotation

Gene Ontology Annotations    

Biological Process

Cellular Component

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Sdf4  (stromal cell derived factor 4)
Stx2  (syntaxin 2)
Stx3  (syntaxin 3)
Stxbp1  (syntaxin binding protein 1)
Stxbp2  (syntaxin binding protein 2)
Syn2  (synapsin II)
Syn3  (synapsin III)


Additional Information