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Eph and Lyn hyper-phosphorylation and CRMP interactions in AD"

Eph and Lyn hyper-phosphorylation and CRMP interactions in AD"
AD中Eph和Lyn过度磷酸化与CRMP相互作用"
批准号:
10746170
负责人:
MATTHIAS BUCK
金额:
$24.15万
依托单位国家:
美国
项目类别:
财政年份:
2023
资助国家:
美国
项目状态:
未结题
起止时间:
2023-07-15 至 2025-06-30

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中文摘要
翻译
Eph受体对心血管和神经元发育中的细胞迁移做出指导决定,
英文摘要
Eph receptors make guidance decisions for cell migration in cardiovascular and neuronal development, disease, and regeneration. Eph receptors are also involved with higher brain functions, memory and learning. A protein that has been associated with Alzheimer’s, Parkinson’s and other neuronal diseases and injuries is the Collapsin Response Mediator Protein (CRMP) which interacts with several kinases and becomes hyper-phosphorylated alongside increased activation of the kinases. The hyper- phosphorylated CRMP then disrupts the formation of actin and microtubule cytoskeletal structures and it thought to impede Aβ and tau clearance. Cytosolic Lyn kinase, a close homologue of Fyn kinase, is known to interact directly with EphA4 and here, for the first time, we show that an EphA family member and EphB2 directly interacts with CRMP. Analogous to another guidance and cell migration system, the Fyn-Plexin-CRMP complex, the Lyn-EphA4-CRMP association is likely to form a complex with Cdk5 and GSK3β kinases, each also involved in Alzheimer’s. The features of the Eph-CRMP and Eph-Lyn interacting interfaces need to be characterized, as they will be potential biomarkers and targets for therapeutic intervention. The proposal has two main aims. Aim 1) seeks to establish the in vitro phosphorylation patters of various kinases on the intracellular domains of EphA4 and –B2 in the presence and absence of CRMP and to further validate the formation of the complex in cells. Aim 2) The effect that the corresponding phosphomimetic/phospho-defective mutations have on the level of activity on these Eph receptor intracellular regions and of the kinases will be studied with purified proteins in vitro. Eventually, using the knowledge from this project, Antibodies or complex-disrupting-peptides may drive the future development of early detection diagnostics and/or therapeutics.
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Hyper phosphorylation and the plexin CRMP scaffold in Alzheimers Disease
  • 批准号:
    10063377
  • 项目类别:
  • 资助金额:
    $44.28万
  • 财政年份:
    2020
  • 负责人:
    MATTHIAS BUCK
  • 依托单位:
Structure and function of plexin - co-receptor interactions
  • 批准号:
    10004656
  • 项目类别:
  • 资助金额:
    $44.7万
  • 财政年份:
    2018
  • 负责人:
    MATTHIAS BUCK
  • 依托单位:
Structure and function of plexin - co-receptor interactions
  • 批准号:
    10246388
  • 项目类别:
  • 资助金额:
    $43.35万
  • 财政年份:
    2018
  • 负责人:
    MATTHIAS BUCK
  • 依托单位:
Structure and function of plexin - co-receptor interactions
  • 批准号:
    9790965
  • 项目类别:
  • 资助金额:
    $44.56万
  • 财政年份:
    2018
  • 负责人:
    MATTHIAS BUCK
  • 依托单位:
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