2002
DOI: 10.1073/pnas.072083499
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Aquaporin 1 regulates GTP-induced rapid gating of water in secretory vesicles

Abstract: The swelling of secretory vesicles has been implicated in exocytosis, but the underlying mechanism of vesicle swelling remains largely unknown. Zymogen granules (ZGs), the membrane-bound secretory vesicles in exocrine pancreas, swell in response to GTP mediated by a Gαi3 protein. Evidence is presented here that the water channel aquaporin-1 (AQP1) is present in the ZG membrane and participates in rapid GTP-induced vesicular water gating and swelling. Isolated ZGs exhibit low basal water permeability. However, … Show more

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Cited by 146 publications
(151 citation statements)
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References 32 publications
(28 reference statements)
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“…Isolated secretory vesicles and reconstituted swelling-competent proteoliposomes have been utilized [13,[20][21][22]49] to determine the mechanism and regulation of vesicle swelling. As previously discussed, isolated ZGs from the exocrine pancreas swell rapidly in response to GTP [20], suggesting rapid water gating into ZGs following exposure to GTP.…”
Section: Expulsion Of Intravesicular Contents At the Cell Plasma Membmentioning
confidence: 99%
See 2 more Smart Citations
“…Isolated secretory vesicles and reconstituted swelling-competent proteoliposomes have been utilized [13,[20][21][22]49] to determine the mechanism and regulation of vesicle swelling. As previously discussed, isolated ZGs from the exocrine pancreas swell rapidly in response to GTP [20], suggesting rapid water gating into ZGs following exposure to GTP.…”
Section: Expulsion Of Intravesicular Contents At the Cell Plasma Membmentioning
confidence: 99%
“…As previously discussed, isolated ZGs from the exocrine pancreas swell rapidly in response to GTP [20], suggesting rapid water gating into ZGs following exposure to GTP. Results from studies demonstrate the presence of the water channel aquaporin-1 (AQP1) at the ZG membrane [21] and its participation in GTP-mediated water entry and vesicle swelling. Further, the molecular regulation of AQP1 at the ZG membrane has been studied [49], providing a general mechanism of secretory vesicle swelling.…”
Section: Expulsion Of Intravesicular Contents At the Cell Plasma Membmentioning
confidence: 99%
See 1 more Smart Citation
“…In this way, the pro-inflammatory role of AQP4 involves a positive feedback cycle of local brain swelling (cytotoxic edema) and secretion of pro-inflammatory cytokines, which at the molecular level rely on AQP4-dependent osmotic water permeability and astrocyte swelling (338). Evidence for involvement of aquaporins in an analogous process, secretory vesicle exocytosis, has been reported (455,456), though the biophysical mechanisms remain speculative on how aquaporin water transport facilitates fusion of secretory vesicles with the cell plasma membrane. The hypothesis of AQP4-mediated cytokine release fits well with PD, which is intimately linked to inflammation and associated with elevated levels of cytokines, both in post mortem PD brains as well as in animal models (120)(121)(122)(123)(124).…”
Section: Selective Vulnerability Mediated By the Glial Microenvironmementioning
confidence: 99%
“…The very process that set that in train was thought to be due to an all-or-none process of dehiscence of synaptic vesicles at the presynaptic membrane. Today we know this as a highly regulated event, with a very high level of sensitivity, not only in nerve synapses, but also in endocytotic vesicle fusion in other forms of secretion, as in acinar cells of the pancreas (Cho et al, 2002).…”
mentioning
confidence: 99%