ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING

内溶酶体转运中 ESCRT 功能的分析

基本信息

  • 批准号:
    10798848
  • 负责人:
  • 金额:
    $ 11.46万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-01-01 至 2025-07-31
  • 项目状态:
    未结题

项目摘要

Abstract The endolysosomal network is the portal by which extracellular material enters the cell. As such, the membranes of the endosomes, phagosomes, and lysosomes that comprise this network face challenges from pathogens and other internalized materials as well as from metabolic and chemical stresses. Consequences of damage vary according to the specific compartment and degree of damage, but extensive lysosomal membrane permeabilization triggers cell death while limited disruption of endosomes and phagosomes by particulate material and pathogens leads to inflammasome activation and ensuing cytokine responses. A widely deployed strategy for removing damaged organelles involves the use of selective autophagy, referred to as lysophagy. Removal is, however, unnecessary if organelles are instead repaired. We recently discovered a new role for the ESCRT (endosomal sorting complex required for transport) machinery in responding to nano- scale disruptions in endolysosomal membranes and promoting their repair. In this project, we are building on this discovery and testing the hypothesis that ESCRTs (and in particular ESCRT-III proteins) play a key role in maintaining endolysosomal integrity and function by recognizing and repairing nanoscale membrane damage. This role for the ESCRT machinery is distinct from its widely recognized function in intralumenal vesicle biogenesis and appears applicable at both the plasma membrane and on internal organelles. Nanoscale damage involves short-lived nm-size pre-pore or pore(s) that reseal or, above a critical threshold, expand to allow unrestrained content exchange. We are using a range of chemical, physical, and biological stressors to define the signals as well as molecular and physical mechanisms underlying ESCRT-mediated repair. The Tecan Spark multimode plate reader requested in this administrative supplement application will allow us to move our assays of endolysosomal membrane stress and organelle resilience from our current low-throughput to a high-throughput format, thereby providing the rigorous and quantitative assessment of endolysosomal resilience to different pharmacologic and genetic stressors needed to complete this project and provide insight into how cells respond to a broad range of physiologic and pathophysiologic membrane stress.
摘要

项目成果

期刊论文数量(7)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Triggered recruitment of ESCRT machinery promotes endolysosomal repair.
  • DOI:
    10.1126/science.aar5078
  • 发表时间:
    2018-04-06
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Skowyra ML;Schlesinger PH;Naismith TV;Hanson PI
  • 通讯作者:
    Hanson PI
Mycobacterium tuberculosis Type VII Secretion System Effectors Differentially Impact the ESCRT Endomembrane Damage Response.
  • DOI:
    10.1128/mbio.01765-18
  • 发表时间:
    2018-11-27
  • 期刊:
  • 影响因子:
    6.4
  • 作者:
    Mittal E;Skowyra ML;Uwase G;Tinaztepe E;Mehra A;Köster S;Hanson PI;Philips JA
  • 通讯作者:
    Philips JA
ESCRT puts its thumb on the nanoscale: Fixing tiny holes in endolysosomes.
  • DOI:
    10.1016/j.ceb.2020.06.002
  • 发表时间:
    2020-08
  • 期刊:
  • 影响因子:
    7.5
  • 作者:
    Bohannon KP;Hanson PI
  • 通讯作者:
    Hanson PI
Mechanism and cellular function of direct membrane binding by the ESCRT and ERES-associated Ca2+-sensor ALG-2.
ESCRT 和 ERES 相关 Ca2 传感器 ALG-2 直接膜结合的机制和细胞功能。
  • DOI:
    10.1101/2023.10.17.562764
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Shukla,Sankalp;Chen,Wei;Rao,Shanlin;Yang,Serim;Ou,Chenxi;Larsen,KevinP;Hummer,Gerhard;Hanson,PhyllisI;Hurley,JamesH
  • 通讯作者:
    Hurley,JamesH
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Phyllis I Hanson其他文献

Phyllis I Hanson的其他文献

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{{ truncateString('Phyllis I Hanson', 18)}}的其他基金

Signal relay during directed cell migration
定向细胞迁移过程中的信号中继
  • 批准号:
    10214472
  • 财政年份:
    2020
  • 资助金额:
    $ 11.46万
  • 项目类别:
Signal relay during directed cell migration
定向细胞迁移过程中的信号中继
  • 批准号:
    10655335
  • 财政年份:
    2020
  • 资助金额:
    $ 11.46万
  • 项目类别:
Signal relay during directed cell migration
定向细胞迁移过程中的信号中继
  • 批准号:
    10436900
  • 财政年份:
    2020
  • 资助金额:
    $ 11.46万
  • 项目类别:
ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING
内溶酶体转运中 ESCRT 功能的分析
  • 批准号:
    10447626
  • 财政年份:
    2017
  • 资助金额:
    $ 11.46万
  • 项目类别:
ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING
内溶酶体转运中 ESCRT 功能的分析
  • 批准号:
    10676296
  • 财政年份:
    2017
  • 资助金额:
    $ 11.46万
  • 项目类别:
ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING
内溶酶体转运中 ESCRT 功能的分析
  • 批准号:
    10683489
  • 财政年份:
    2017
  • 资助金额:
    $ 11.46万
  • 项目类别:
ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING
内溶酶体转运中 ESCRT 功能的分析
  • 批准号:
    9264291
  • 财政年份:
    2017
  • 资助金额:
    $ 11.46万
  • 项目类别:
Tracking Intracellular Pathways to Abeta Generation
追踪 Abeta 生成的细胞内途径
  • 批准号:
    9264170
  • 财政年份:
    2017
  • 资助金额:
    $ 11.46万
  • 项目类别:
ANALYSIS OF ESCRT FUNCTION IN ENDOLYSOSOMAL TRAFFICKING
内溶酶体转运中 ESCRT 功能的分析
  • 批准号:
    10299123
  • 财政年份:
    2017
  • 资助金额:
    $ 11.46万
  • 项目类别:
NANOSCALE ARCHITECTURE OF ESCRT MACHINERY IN HIV RELEASE
HIV 释放中 ESCRT 机器的纳米级架构
  • 批准号:
    8993494
  • 财政年份:
    2015
  • 资助金额:
    $ 11.46万
  • 项目类别:
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