Effects of selective endocrine or exocrine induction of AR42J on SNARE and Munc18 protein expression.
OBJECTIVE
We used the amphicrine AR42J as an excellent model to study the differentiation of the secretory machinery of pancreatic endocrine and exocrine cells. Dexamethasone treatment induced the AR42J to differentiate towards the exocrine phenotype capable of secreting amylase in response to cholecystokinin. In contrast, activin A plus hepatocyte growth factor treatment of a subclone of AR42J, AR42J-B13, induced this cell to differentiate morphologically and functionally toward an insulin-containing and insulin-secreting endocrine phenotype. We took advantage of these unique properties of selective exocrine and endocrine induction of the AR42J to reveal which distinct combinations of exocytic SNARE complex proteins (syntaxin, SNAP-25 and VAMP) and associated Munc18 proteins were preferentially expressed to play a role in enzyme and insulin secretion.


CONCLUSIONS
To our surprise, both endocrine and exocrine induction of AR42J and AR42J-B13 caused very similar upregulation in the expression of the exocytic member isoforms of the syntaxin, SNAP-25, VAMP, and Munc18 families. We conclude that whereas the differentiation of the proximal components of the secretory machinery of the exocrine acinar and endocrine islet beta-cells is distinct, the differentiation of the distal components of exocytosis between these two cell types is very similar.
Huang
Xiaohang
X
Department of Medicine, University of Toronto, Toronto, Ontario, Canada.
Sheu
Laura
L
Kang
Youhou
Y
Eto
Yuzuru
Y
Kojima
Itaru
I
Gaisano
Herbert Y
HY
D028341:Activins / Q000494:pharmacology; D000681:Amylases / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D003907:Dexamethasone / Q000494:pharmacology; D017228:Hepatocyte Growth Factor / Q000494:pharmacology; D028322:Inhibin-beta Subunits / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D008565:Membrane Proteins / Q000096:biosynthesis*; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins / Q000096:biosynthesis; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D014176:Protein Biosynthesis; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D015854:Up-Regulation; D033921:Vesicular Transport Proteins
D007328:Insulin; D008565:Membrane Proteins; D051938:Munc18 Proteins; D009419:Nerve Tissue Proteins; D050765:Qa-SNARE Proteins; D050683:R-SNARE Proteins; D050825:Synaptosomal-Associated Protein 25; D033921:Vesicular Transport Proteins; C422405:activin A; D028341:Activins; D017228:Hepatocyte Growth Factor; D003907:Dexamethasone; D028322:Inhibin-beta Subunits; D000681:Amylases