SNARE HYPOTHESIS AT NERVE ENDINGS
神经末梢的圈套假设
基本信息
- 批准号:6126338
- 负责人:
- 金额:$ 21.32万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1997
- 资助国家:美国
- 起止时间:1997-12-01 至 2002-11-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION: (Investigator's Abstract): Many key proteins involved in
membrane targeting and synaptic vesicle neurotransmitter release have been
identified and a fundamental set of interactions defined and placed in a
model termed the SNARE hypothesis. However, despite recent rapid progress
in identifying molecular components of the membrane targeting and fusion
machine, regulatory influences facilitating or inhibiting the protein
interactions or the sequence of interactions remain poorly defined. It is
the long range goal of the proposed research to identify and understand the
regulatory mechanism(s) which govern SNARE protein interactions and,
thereby, regulate neurotransmitter and neurohormone release and synaptic
plasticity. Preliminary molecular/biochemical studies combined with
functional studies monitoring membrane capacitance changes, as a measure of
exo-endocytotic activity under whole cell patch clamp, have indicated that
proteins of the Sec1 family serve an important regulatory control function.
Experiments proposed will test the hypothesis that nSec1 protein (nSec1p)
regulates neurosecretion via a specific regulated interaction with syntaxins
and that this interaction enhances secretory granule docking. The proposed
experiments will utilize nerve endings of the hypothalamo-neurohypophysial
system, which possess unique anatomical and electrophysiological advantages
allowing resolution of the molecular events of the secretory process at
nerve endings to be studied in greater detail than at any other nerve
endings. The investigators will utilize a combination of molecular,
biochemical, and patch clamp techniques to characterize the regulation of
nSec1 protein interactions and to analyze functional effects on Ca2+
currents and on the amplitude and kinetics of secretion with msec resolution
at individual nerve endings. The specific aims are: 1) to determine the
sites of phosphorylation on nSec1p and examine regulation of protein
interactions by specific kinase activity and depolarizing stimuli, 2) to
determine the mechanism by which nSec1p regulates secretory granule
exocytosis and elucidate the effects of phosphorylation state on secretion,
3) to determine if nSec1p regulation of exocytosis utilizes the molecular
mechanisms and machinery proposed by the SNARE hypothesis, and 4) to
determine if nSec1p interacts with and activates cdk5, whether this
interaction is regulated by nSec1p phosphorylation, and if there are
functional consequences on secretion. In summary, an understanding of the
mechanisms by which nSec1p regulates SNARE protein interactions may be
essential to full understanding of both short and long-term processes of
synaptic plasticity and memory.
描述:(研究者摘要):许多关键蛋白参与
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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EDWARD L STUENKEL其他文献
EDWARD L STUENKEL的其他文献
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{{ truncateString('EDWARD L STUENKEL', 18)}}的其他基金
Trans-synaptic control of presynaptic neurotransmitter release
突触前神经递质释放的跨突触控制
- 批准号:
9284531 - 财政年份:2016
- 资助金额:
$ 21.32万 - 项目类别:
Trans-synaptic control of presynaptic neurotransmitter release
突触前神经递质释放的跨突触控制
- 批准号:
9158582 - 财政年份:2016
- 资助金额:
$ 21.32万 - 项目类别:
Mechanisms of Rab27 regulation of insulin secretion
Rab27调节胰岛素分泌的机制
- 批准号:
8007206 - 财政年份:2010
- 资助金额:
$ 21.32万 - 项目类别:
Mechanisms of Rab27 regulation of insulin secretion
Rab27调节胰岛素分泌的机制
- 批准号:
8228165 - 财政年份:2009
- 资助金额:
$ 21.32万 - 项目类别:
Mechanisms of Rab27 regulation of insulin secretion
Rab27调节胰岛素分泌的机制
- 批准号:
7579533 - 财政年份:2009
- 资助金额:
$ 21.32万 - 项目类别:
Mechanisms of Rab27 regulation of insulin secretion
Rab27调节胰岛素分泌的机制
- 批准号:
8019594 - 财政年份:2009
- 资助金额:
$ 21.32万 - 项目类别:
Mechanisms of Rab27 regulation of insulin secretion
Rab27调节胰岛素分泌的机制
- 批准号:
7868572 - 财政年份:2009
- 资助金额:
$ 21.32万 - 项目类别:
Regulation of tomosyn-SNARE complex assembly in neurosecretion
神经分泌中 tomosyn-SNARE 复合体组装的调节
- 批准号:
7624207 - 财政年份:2006
- 资助金额:
$ 21.32万 - 项目类别:
Mechanisms of Rab27 regulation of insulin secretion
Rab27调节胰岛素分泌的机制
- 批准号:
7281375 - 财政年份:2006
- 资助金额:
$ 21.32万 - 项目类别:
Regulation of tomosyn-SNARE complex assembly in neurosecretion
神经分泌中 tomosyn-SNARE 复合体组装的调节
- 批准号:
7145476 - 财政年份:2006
- 资助金额:
$ 21.32万 - 项目类别:
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