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Title: An investigation of the mechanism of secretion in the pancreatic acinar cell
Author: Hansen, N.
Awarding Body: University of Cambridge
Current Institution: University of Cambridge
Date of Award: 2000
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The aim of this research has been to investigate the role of SNARE proteins and the zymogen granule protein syncollin in secretion. Using isoform-specific anti-syntaxin antisera, syntaxins 2 and 4 have been localised to the plasma membrane of the acinar cell, whilst syntaxin 3, together with the R-SNARE VAMP-2, is present on zymogen granules. Using the clostridial neurotoxins and an in vitro dequenching assay to measure membrane fusion, BoNT-C sensitive syntaxin 2 has been implicated in the fusion of zymogen granules with the plasma membrane. Syntaxin 3 has also been proposed to mediate a homotypic granule-granule fusion event, which may represent compound exocytosis in vivo. VAMP-2 and syntaxin 4 appear not to play major roles in either of these fusion events. Syncollin was originally identified as a zymogen granule membrane protein purified as syntaxin 1 binding protein. Recombinant syncollin in vitro specifically binds syntaxins 1 and 2 in taurodeoxycholate extracts of membrane, while recombinant fragments of the full-length syncollin molecule inhibit Ca2+-dependent fusion in the in vitro dequenching assay. This inhibition correlates with the in vitro binding pattern of the fragments to syntaxin 2 but not to syntaxin 1, implying that inhibition is mediated by a specific interaction with plasma membrane syntaxin 2. Studies on the in vivo nature of syncollin identified two populations within the granule, one lumenal and one membrane-associated. Sucrose density gradient data suggest that membrane-bound syncollin exists as a higher order homo-oligomer, and structural studies of purified syncollin suggest that oligomeric syncollin forms a pore-like structure. In the light of these data, a modified role for syncollin in secretion will be discussed.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available