Function of a Novel Matrix Junction in Endothelial Cells
Function of a Novel Matrix Junction in Endothelial Cells
批准号:
6621107
负责人:
JONATHAN C. JONES
金额:
$29.26万
依托单位国家:
美国
项目类别:
财政年份:
2002
资助国家:
美国
项目状态:
已结题
起止时间:
2002-01-01 至 2005-12-31
中文摘要
描述(申请人提供):血管的管腔内衬有
内皮细胞(ECs)。后者位于基底膜上,其结构
元素包括层粘连蛋白、蛋白多糖和胶原蛋白。ECS与这些服务器进行交互
基质蛋白部分通过被称为整合素的受体。这样的互动是
参与调节包括黏附在内的许多细胞功能,
运动性和基因表达。在成人,血管中的内皮细胞
都是静止的。然而,在伤口愈合和病理条件下
包括癌症和炎症性疾病在内,刺激会激活新的血管
生长,这一过程被称为血管生成。在这个应用程序中,我们的研究是
聚焦于我们最近在内皮细胞中发现的一种新的基质连接。
初步实验表明,内皮细胞组装了一个新的焦点
与微丝和微丝都有联系的接触式结构
细胞骨架中的波形。这种波形蛋白相关的基质黏附(VMA)
在其核心拥有avbeta3整合素异源二聚体和A4层粘连蛋白
细胞外基质中含有亚基的配体。此外,VMA
其特征是含有我们推测涉及的plectin
介导细胞表面对波形蛋白细胞骨架的锚定。这个交叉口
以依赖于生长因子的方式组装,并似乎在EC中发挥作用
迁移和分支形态发生,血管生成的基本要素,
由于针对avbeta3整合素异源二聚体和A4的抗体
层粘连蛋白亚单位抑制这些事件。在目标1中,我们将进一步承诺
VMA分子组成的表征
强调其蛋白质成分是如何相互作用的,以及如何识别
与细胞内波形蛋白细胞骨架锚定有关的分子
浮出水面。在目标2中,我们将研究VMA在生活中的组装动力学
在ECS中,我们表达了绿色荧光标记的VMA蛋白
蛋白。在目标3中,我们将分析虚拟MA的组件(S)在
体内血管生成。这些研究将为我们提供新的视角,了解
整合素/基质在血管生成中的相互作用。
英文摘要
DESCRIPTION (provided by the applicant): The lumen of blood vessels is lined by
endothelial cells (ECs). The latter lie on a basement membrane whose structural
elements include laminins, proteoglycans and collagens. ECs interact with these
matrix proteins, in part, via receptors called integrins. Such interactions are
involved in regulating a number of cellular functions including adhesion,
motility and gene expression. In the adult, endothelial cells in the vessels
are quiescent. However, in wound healing and in pathological conditions
including cancer and inflammatory diseases, a stimulus activates new vessel
growth, a process called angiogenesis. In this application, our studies are
focused on a novel matrix junction that we recently identified in ECs.
Preliminary experiments indicate that endothelial cells assemble a novel focal
contact-like structure that is associated with both the microfilament and
vimentin cytoskeletons. This vimentin-associated matrix adhesion (VMA)
possesses, at its core, the avbeta3 integrin heterodimer and an a4 laminin
subunit-containing ligand in the extracellular matrix. In addition, the VMA
characteristically contains plectin that we hypothesize is involved in
mediating cell surface anchorage of the vimentin cytoskeleton. This junction
assembles in a growth factor-dependent manner and appears to play a role in EC
migration and branching morphogenesis, essential elements of angiogenesis,
since antibodies against both the avbeta3 integrin heterodimer and the a4
laminin subunit inhibit these events. In aim 1, we will undertake further
characterization of the molecular composition of the VMA with particular
emphasis on how its protein components interact and on identification of the
molecules involved in anchorage of the vimentin cytoskeleton at the cell
surface. In aim 2, we will study the dynamics of assembly of the VMA in living
ECs in which we have expressed VMA proteins tagged with green fluorescent
protein. In aim 3, we will analyze the function(s) of components of the VMA in
angiogenesis in vivo. These studies will provide new insight into the role of
integrin/matrix interactions in angiogenesis.
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会议论文
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批准号:7435396
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资助金额:$32.88万
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财政年份:2007
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批准号:6863749
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批准号:6713311
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资助金额:$3.84万
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Function of a Novel Matrix Junction in Endothelial Cells
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批准号:6430560
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资助金额:$31.76万
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财政年份:2002
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负责人:JONATHAN C. JONES
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Function of a Novel Matrix Junction in Endothelial Cells
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批准号:6831669
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资助金额:$29.26万
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财政年份:2002
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负责人:JONATHAN C. JONES
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依托单位:
Function of a Novel Matrix Junction in Endothelial Cells
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批准号:6688282
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项目类别:
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资助金额:$29.26万
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财政年份:2002
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负责人:JONATHAN C. JONES
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依托单位:
LAMININ-5 AND HEMIDESMOSOMES IN ORAL EPITHELIAL CELLS
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批准号:6323346
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项目类别:
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资助金额:$19.56万
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财政年份:2000
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负责人:JONATHAN C. JONES
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依托单位:
LAMININ-5 AND HEMIDESMOSOMES IN ORAL EPITHELIAL CELLS
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批准号:6324662
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项目类别:
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资助金额:$22.13万
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财政年份:2000
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负责人:JONATHAN C. JONES
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依托单位:
LAMININ-5 AND HEMIDESMOSOMES IN ORAL EPITHELIAL CELLS
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项目类别:
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资助金额:$19.56万
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财政年份:1999
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负责人:JONATHAN C. JONES
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依托单位:
LAMININ-5 AND HEMIDESMOSOMES IN ORAL EPITHELIAL CELLS
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批准号:6104950
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项目类别:
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资助金额:$18.42万
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财政年份:1999
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负责人:JONATHAN C. JONES
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依托单位:
LAMININ-5 AND HEMIDESMOSOMES IN ORAL EPITHELIAL CELLS
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批准号:6270372
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项目类别:
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资助金额:$17.4万
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财政年份:1998
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负责人:JONATHAN C. JONES
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依托单位:
LAMININ-5 AND HEMIDESMOSOMES IN ORAL EPITHELIAL CELLS
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资助金额:$12.87万
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财政年份:1997
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负责人:JONATHAN C. JONES
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依托单位:
Junctions, Cytoskeleton & Matrix of the Oral Epithelium
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批准号:6622961
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资助金额:$110.26万
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财政年份:1997
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依托单位:
Junctions, Cytoskeleton & Matrix of the Oral Epithelium
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资助金额:$113.26万
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财政年份:1997
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依托单位:
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财政年份:1997
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负责人:JONATHAN C. JONES
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依托单位:
Junctions, Cytoskeleton & Matrix of the Oral Epithelium
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批准号:7008179
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资助金额:$116.94万
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财政年份:1997
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负责人:JONATHAN C. JONES
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依托单位:
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财政年份:1997
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负责人:JONATHAN C. JONES
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依托单位:
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资助金额:$6.42万
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财政年份:1997
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负责人:JONATHAN C. JONES
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依托单位:
海外基金