Control of membrane fusion dynamics during regulated exocytosis.

Abstract:

:The study of regulated exocytosis uniquely allows the direct measurement of intracellular membrane fusion events in real time. We have exploited this to examine factors that regulate not only the extent but also the dynamics of single fusion/release events. The general strategy used has been to assess exocytosis in transiently transfected PC12 or adrenal chromaffin cells. We aimed to design mutant constructs based on in vitro biochemistry, in some cases informed by knowledge of protein structure. Using this approach we have demonstrated an inhibitory role for the putative Rab3 effector Noc2 that requires interaction with Rab3. Using carbon-fibre amperometry on adrenal chromaffin cells, we have demonstrated regulation of the kinetics of single granule release events consistent with changes in fusion pore dynamics and switches between full fusion and 'kiss-and-run' fusion. These studies have demonstrated a late role for cysteine string protein in exocytosis. In addition, they have focused attention on a key role for Munc18 in the regulation of post-fusion events that affect fusion pore dynamics.

journal_name

Biochem Soc Trans

authors

Burgoyne RD,Fisher RJ,Graham ME,Haynes LP,Morgan A

doi

10.1042/bst0290467

keywords:

subject

Has Abstract

pub_date

2001-08-01 00:00:00

pages

467-72

issue

Pt 4

eissn

0300-5127

issn

1470-8752

journal_volume

29

pub_type

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