The myosin VI interactome: the role of motor cargo/adaptor complexes and ubiquitin-binding during selective autophagy
The myosin VI interactome: the role of motor cargo/adaptor complexes and ubiquitin-binding during selective autophagy
批准号:
MR/K000888/1
负责人:
Folma Buss
金额:
$63.95万
依托单位:
依托单位国家:
英国
项目类别:
Research Grant
财政年份:
2013
资助国家:
英国
项目状态:
已结题
起止时间:
2013 至 --
中文摘要
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英文摘要
A significant proportion of our ageing population is affected by the late onset of neurodegenerative disorders such as Alzheimer's, motor neuron or Parkinson's diseases. A better understanding of what causes these neurodegenerative diseases could lead to new therapeutic and preventive strategies or could at least improve the quality of life of the affected patients. More and more research now suggests that motor neuron disease and some forms of dementia are linked to defects in a cellular pathway that is used to digest abnormal proteins or defective parts of the cell. These defects can lead to an accumulation of these protein as large clumps, which may clog up the transport of essential cargo along nerves in our limbs and eventually cause the nerve cells to die. Our research is focused on the special molecular motor protein myosin VI, which drives cargo along tracks in the opposite direction to all other motors to specific sites in the cell, rather like a train running along a railway network to its specific destinations. The cargo is hooked up to the motor with the help of specific adaptor proteins that we have identified in our research. New results now show that this motor protein is present on protein lumps found in nerve cells from patients that died from Alzheimer's disease. Furthermore, it was recently shown that mistakes (mutations) in the protein optineurin, which links myosin VI to specific cargos, causes an inherited form of motor neuron disease. We will thus explore whether myosin VI and optineurin move and dispose of these toxic protein lumps and prevent their accumulation to avoid the death of nerve cells and subsequent neurodegenerative diseases.We thus hope to identify the precise roles of myosin VI and its adaptor proteins in the pathway that is important for clearance of protein aggregates to keep the nerve cells healthy. This will open up new areas of research that may guide future clinical studies and the development of potential diagnostic tools and possible therapeutic strategies.
期刊论文(10)
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MYO6 is targeted by $\textit{Salmonella}$ virulence effectors to trigger PI3-kinase signaling and pathogen invasion into host cells
MYO6 被 $ extit{沙门氏菌}$ 毒力效应子靶向,触发 PI3 激酶信号传导和病原体入侵宿主细胞
DOI:
10.17863/cam.9636
发表时间:
2017
期刊:
影响因子:
--
作者:
[Brooks A]
通讯作者:
Brooks A
DOI:
10.1073/pnas.1616418114
发表时间:
2017-04-11
期刊:
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
影响因子:
11.1
作者:
[Brooks, Andrew B. E., Humphreys, Daniel, Koronakis, Vassilis]
通讯作者:
Koronakis, Vassilis
Myosin VI maintains the actin-dependent organization of the tubulobulbar complexes required for endocytosis during mouse spermiogenesis
肌球蛋白 VI 维持小鼠精子发生过程中内吞作用所需的肌动蛋白依赖性管球复合体组织
DOI:
10.17863/cam.47695
发表时间:
2020
期刊:
影响因子:
--
作者:
[Buss F]
通讯作者:
Buss F
DOI:
10.1242/dmm.017368
发表时间:
2014-12
期刊:
Disease models & mechanisms
影响因子:
4.3
作者:
[Brandstaetter H, Kruppa AJ, Buss F]
通讯作者:
Buss F
DOI:
10.1042/bcj20160571
发表时间:
2016-10-01
期刊:
The Biochemical journal
影响因子:
--
作者:
[Arden SD, Tumbarello DA, Butt T, Kendrick-Jones J, Buss F]
通讯作者:
Buss F
共 7 条
Spatial and temporal mechanisms controlling diverse myosin motor functions in health and disease
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批准号:MR/S007776/1
-
项目类别:Research Grant
-
资助金额:$184.37万
-
财政年份:2019
-
负责人:Folma Buss
-
依托单位:
Defining the role of myosin motor proteins and their cargo adaptors in cytokine secretion
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资助金额:$47.23万
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Investigating the role of Myosin VI in quality control of mitochondria linked to Parkinson's disease pathology
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项目类别:Research Grant
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资助金额:$68.96万
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负责人:Folma Buss
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依托单位:
Regulation of myosin VI motor activity by cargo binding in vivo and in vitro
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批准号:BB/K001981/1
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项目类别:Research Grant
-
资助金额:$61.21万
-
财政年份:2013
-
负责人:Folma Buss
-
依托单位:
国内基金
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