Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 102, Issue 14, Pages 5204-5209Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0501412102
Keywords
exocytosis; fusion pore; granule; phosphatidylinositol-4,5-bisphosphate; secretion
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Funding
- NIDDK NIH HHS [DK45735, P30 DK045735] Funding Source: Medline
- NINDS NIH HHS [NS36251, R37 NS036251, R01 NS036251] Funding Source: Medline
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Phosphatidylinositol-4,5-bisphosphate was proposed to be an important regulator of large dense-core vesicle exocytosis from neuroendocrine tissues. Here, we have examined the kinetics of secretion in chromaffin cells from mice lacking phosphatidylinositol phosphate kinase type l gamma, the major neuronal phosphatidylinositol-4-phosphate 5-kinase. Absence of this enzyme caused a reduction of the readily releasable vesicle pool and its refilling rate, with a small increase in morphologically docked vesicles, indicating a defect in vesicle priming. Furthermore, amperometry revealed a delay in fusion pore expansion. These results provide direct genetic evidence for a key role of phosphatidylinositol-4,5-bisphosphate synthesis in the regulation of large dense-core vesicle fusion dynamics.
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