Syncollin is a 13 kDa protein that is highly expressed in the exocrine pancreas. Syncollin normally exists as a doughnut-shaped homo-oligomer (quite probably a hexamer) in close association with the luminal surface of the zymogen granule membrane. In the present study, we examine the effect of expression of syncollin in AtT-20 neuroendocrine cells, which do not normally express this protein. Efficient expression was achieved by infection of the cells with adenoviral constructs encoding either untagged or GFP (green fluorescent protein)-tagged syncollin. Both forms of the protein were sorted into corticotropin (ACTH)-positive secretory vesicles present mainly at the tips of cell processes. Neither form affected basal corticotropin secretion or the constitutive secretion of exogenously expressed secreted alkaline phosphatase. In contrast, regulated secretion of corticotropin was inhibited (by 49%) by untagged but not by GFP-tagged syncollin. In parallel, untagged syncollin caused a 46% reduction in the number of secretory vesicles present at the tips of the cell processes. Syncollin–GFP was without effect. We could also show that native syncollin purified from rat pancreas was capable of permeabilizing erythrocytes. We suggest that syncollin may induce uncontrolled permeabilization of corticotropin-containing vesicles and subsequently destabilize them. Both forms of syncollin were tightly membrane-associated and appeared to exist as homooligomers. Hence, the lack of effect of syncollin–GFP on regulated exocytosis suggests that the GFP tag interferes in a subtler manner with the properties of the assembled protein.
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Research Article|
June 15 2004
Syncollin inhibits regulated corticotropin secretion from AtT-20 cells through a reduction in the secretory vesicle population
Barbara WÄSLE;
Barbara WÄSLE
*Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
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Lori B. HAYS;
Lori B. HAYS
†Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, U.S.A.
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Christopher J. RHODES;
Christopher J. RHODES
†Pacific Northwest Research Institute, 720 Broadway, Seattle, WA 98122, U.S.A.
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J. Michael EDWARDSON
J. Michael EDWARDSON
1
*Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, U.K.
1To whom correspondence should be addressed (e-mail jme1000@cam.ac.uk).
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Publisher: Portland Press Ltd
Received:
November 13 2003
Revision Received:
March 23 2004
Accepted:
March 24 2004
Accepted Manuscript online:
March 24 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London ©2004
2004
Biochem J (2004) 380 (3): 897–905.
Article history
Received:
November 13 2003
Revision Received:
March 23 2004
Accepted:
March 24 2004
Accepted Manuscript online:
March 24 2004
Citation
Barbara WÄSLE, Lori B. HAYS, Christopher J. RHODES, J. Michael EDWARDSON; Syncollin inhibits regulated corticotropin secretion from AtT-20 cells through a reduction in the secretory vesicle population. Biochem J 15 June 2004; 380 (3): 897–905. doi: https://doi.org/10.1042/bj20031726
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