Release and retrieval of dense-core granule proteins in hippocampal neurons

海马神经元致密核心颗粒蛋白的释放和恢复

基本信息

  • 批准号:
    7253866
  • 负责人:
  • 金额:
    $ 20.03万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2000
  • 资助国家:
    美国
  • 起止时间:
    2000-09-01 至 2012-06-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Several proteins that have been implicated prominently in long-term potentiation (LTP), a cellular model of learning, are housed in dense-core granules (DCGs) in neurons of the hippocampus and are secreted from these neurons by regulated exocytosis of DCGs. DCGs in hippocampal neurons, and neuronal DCGs generally, have not been well studied, despite their importance as organelles that store, transport, and mediate secretion of critical proteins. Moreover, our recent data highlight significant differences between DCGs in hippocampal neurons and their better-studied neuroendocrine counterparts. In light of this, we propose experiments directed at determining mechanisms underlying two pivotal processes that bear on LTP: the release and retrieval of DCG cargo proteins in hippocampal neurons. Our studies will involve direct visualization of protein release from individual DCGs localized at post-synaptic and other subcellular sites. The major goals of Specific Aim 1 are to determine exocytotic mechanisms used by DCGs in hippocampal neurons, and associated protein release kinetics, induced by a spectrum of electrical stimulation paradigms, including those linked to LTP. The major goals of Specific Aim 2 are to determine mechanisms underlying retrieval of DCG proteins induced by a spectrum of stimulation paradigms, and to determine if a previously fused DCG that is retrieved relatively intact and retains protein will fuse again and release retained protein. Our results will elucidate release and retrieval processes that are implicated in the regulation of DCG protein release, in the facilitation of DCG protein reuse, and in the modulation of release and retrieval of DCG proteins to meet the demands of different inputs. Moreover, our results will provide fundamental insight into cellular processes that may underlie LTP and will reveal behavior of a DCG protein that has been implicated in physiological and pathological functions in the nervous system, including learning, memory, and neurotoxicity associated with Alzheimer's disease. The studies in this proposal focus on elucidating mechanisms underlying the release and retrieval of dense-core granule proteins in hippocampal neurons. The results will provide fundamental insight into cellular processes that may underlie long-term potentiation, a cellular model of learning, and will elucidate the behavior of tissue plasminogen activator, a dense-core granule protein that has been implicated in physiological and pathological functions in the nervous system, including learning, memory, and neurotoxicity associated with Alzheimer's disease.
描述(由申请人提供):在长时程增强(LTP)(一种学习的细胞模型)中有显著牵连的几种蛋白质被容纳在海马神经元的致密核心颗粒(DCG)中,并通过DCG的调节胞吐作用从这些神经元中分泌。海马神经元中的DCG和一般的神经元DCG尚未得到很好的研究,尽管它们作为储存、运输和介导关键蛋白质分泌的细胞器很重要。此外,我们最近的数据突出了海马神经元中的DCG与其更好研究的神经内分泌对应物之间的显着差异。有鉴于此,我们提出了实验,旨在确定两个关键过程,承担LTP的机制:在海马神经元中的DCG货物蛋白的释放和检索。我们的研究将涉及直接可视化的蛋白质释放从个别DCG定位在突触后和其他亚细胞网站。具体目标1的主要目标是确定海马神经元中DCG使用的胞吐机制,以及相关的蛋白质释放动力学,由一系列电刺激范例诱导,包括与LTP相关的那些。具体目标2的主要目标是确定由刺激范例的频谱诱导的DCG蛋白质的恢复的潜在机制,并确定是否先前融合的DCG相对完整地恢复并保留蛋白质将再次融合并释放保留的蛋白质。我们的研究结果将阐明释放和检索过程中涉及的DCG蛋白释放的调节,在促进DCG蛋白的再利用,并在释放和检索的DCG蛋白的调制,以满足不同的输入的需求。此外,我们的结果将为可能构成LTP的细胞过程提供基本见解,并揭示与神经系统生理和病理功能有关的DCG蛋白的行为,包括与阿尔茨海默病相关的学习、记忆和神经毒性。本研究的重点是阐明海马神经元致密核心颗粒蛋白释放和回收的机制。这些结果将提供对细胞过程的基本了解,这些细胞过程可能是长时程增强的基础,这是一种学习的细胞模型,并将阐明组织纤溶酶原激活剂的行为,组织纤溶酶原激活剂是一种致密核心颗粒蛋白,与神经系统的生理和病理功能有关,包括学习,记忆和与阿尔茨海默病相关的神经毒性。

项目成果

期刊论文数量(8)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Hindered submicron mobility and long-term storage of presynaptic dense-core granules revealed by single-particle tracking.
  • DOI:
    10.1002/dneu.20984
  • 发表时间:
    2012-09
  • 期刊:
  • 影响因子:
    3
  • 作者:
    Scalettar, B. A.;Jacobs, C.;Fulwiler, A.;Prahl, L.;Simon, A.;Hilken, L.;Lochner, J. E.
  • 通讯作者:
    Lochner, J. E.
Sweeping model of dynamin activity. Visualization of coupling between exocytosis and endocytosis under an evanescent wave microscope with green fluorescent proteins.
动力活动的扫除模型。
  • DOI:
    10.1074/jbc.c200051200
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Tsuboi,Takashi;Terakawa,Susumu;Scalettar,BetheA;Fantus,Claire;Roder,John;Jeromin,Andreas
  • 通讯作者:
    Jeromin,Andreas
Stochastic Subcellular Organization of Dense-Core Vesicles Revealed by Point Pattern Analysis.
  • DOI:
    10.1016/j.bpj.2016.07.019
  • 发表时间:
    2016-08
  • 期刊:
  • 影响因子:
    3.4
  • 作者:
    Benjamin J Robinson;Bogdan Stanisavljevic;M. Silverman;B. Scalettar
  • 通讯作者:
    Benjamin J Robinson;Bogdan Stanisavljevic;M. Silverman;B. Scalettar
Neuronal calcium sensor-1 binds to regulated secretory organelles and functions in basal and stimulated exocytosis in PC12 cells.
神经元钙传感器-1 与受调节的分泌细胞器结合,并在 PC12 细胞的基础胞吐作用和刺激胞吐作用中发挥作用。
  • DOI:
    10.1242/jcs.115.11.2399
  • 发表时间:
    2002
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Scalettar,BetheA;Rosa,Patrizia;Taverna,Elena;Francolini,Maura;Tsuboi,Takashi;Terakawa,Susumu;Koizumi,Schuichi;Roder,John;Jeromin,Andreas
  • 通讯作者:
    Jeromin,Andreas
Efficient copackaging and cotransport yields postsynaptic colocalization of neuromodulators associated with synaptic plasticity.
  • DOI:
    10.1002/dneu.20650
  • 发表时间:
    2008-09-01
  • 期刊:
  • 影响因子:
    3
  • 作者:
    Lochner, J. E.;Spangler, E.;Chavarha, M.;Jacobs, C.;McAllister, K.;Schuttner, L. C.;Scalettar, B. A.
  • 通讯作者:
    Scalettar, B. A.
{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

BETHE A SCALETTAR其他文献

BETHE A SCALETTAR的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('BETHE A SCALETTAR', 18)}}的其他基金

SORTING AND POST-GOLGI TRANSPORT OF TPA
TPA 的分选和高尔基后运输
  • 批准号:
    6159604
  • 财政年份:
    2000
  • 资助金额:
    $ 20.03万
  • 项目类别:

相似海外基金

AcT-Cog: Online cognitive assessment in the Alteplase compared to Tenecteplase (AcT) trial.
AcT-Cog:阿替普酶与替奈普酶 (AcT) 试验相比的在线认知评估。
  • 批准号:
    444794
  • 财政年份:
    2021
  • 资助金额:
    $ 20.03万
  • 项目类别:
    Operating Grants
INTERRAcT: Thrombus characteristics for predicting Reperfusion with Alteplase compared to Tenecteplase
INTERRAcT:与替奈普酶相比,阿替普酶预测再灌注的血栓特征
  • 批准号:
    433102
  • 财政年份:
    2020
  • 资助金额:
    $ 20.03万
  • 项目类别:
    Operating Grants
Alteplase Compared to Tenecteplase in patients with Acute Ischemic Stroke: QuICR & OPTIMISE Registry based Pragmatic Randomized Controlled Trial
阿替普酶与替奈普酶治疗急性缺血性中风患者的比较:QuICR
  • 批准号:
    401715
  • 财政年份:
    2019
  • 资助金额:
    $ 20.03万
  • 项目类别:
    Operating Grants
Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE) Trial
替奈普酶与阿替普酶用于中风溶栓评估 (TASTE) 试验
  • 批准号:
    nhmrc : 1079696
  • 财政年份:
    2015
  • 资助金额:
    $ 20.03万
  • 项目类别:
    Project Grants
Tenecteplase versus Alteplase for Stroke Thrombolysis Evaluation (TASTE) Trial
替奈普酶与阿替普酶用于中风溶栓评估 (TASTE) 试验
  • 批准号:
    nhmrc : GNT1079696
  • 财政年份:
    2015
  • 资助金额:
    $ 20.03万
  • 项目类别:
    Project Grants
Low-Dose Tenecteplase vs Standard-Dose Alteplase for Acute Ischaemic Stroke: An Imaging Based Safety and Efficacy Study
低剂量替奈普酶与标准剂量阿替普酶治疗急性缺血性中风:一项基于影像学的安全性和有效性研究
  • 批准号:
    nhmrc : 510722
  • 财政年份:
    2008
  • 资助金额:
    $ 20.03万
  • 项目类别:
    NHMRC Project Grants
Treament of Deep Vein Thrombosis with Alteplase
阿替普酶治疗深静脉血栓
  • 批准号:
    7004919
  • 财政年份:
  • 资助金额:
    $ 20.03万
  • 项目类别:
Treatment of Deep Vein Thrombosis of the Lower Extremities w/Low Dose Alteplase
小剂量阿替普酶治疗下肢深静脉血栓
  • 批准号:
    8565339
  • 财政年份:
  • 资助金额:
    $ 20.03万
  • 项目类别:
Treament of Deep Vein Thrombosis of the Lower Extremities w/Low Dose Alteplase
小剂量阿替普酶治疗下肢深静脉血栓
  • 批准号:
    7593114
  • 财政年份:
  • 资助金额:
    $ 20.03万
  • 项目类别:
Treatment of Deep Vein Thrombosis of the Lower Extremities w/Low Dose Alteplase
小剂量阿替普酶治疗下肢深静脉血栓
  • 批准号:
    8952839
  • 财政年份:
  • 资助金额:
    $ 20.03万
  • 项目类别:
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了