MOLECULAR SORTING DURING INTRACELLULAR TRANSPORT
细胞内运输过程中的分子分选
基本信息
- 批准号:2175618
- 负责人:
- 金额:$ 25.01万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:1981
- 资助国家:美国
- 起止时间:1981-07-01 至 1999-06-30
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The plasma membranes of many mammalian cells are differentiated into
biochemically and functionally distinct. This asymmetric arrangement of
membrane components is best understood in the case of epithelial cells,
whose surfaces are polarized into apical and basolateral domains that
allow epithelia to serve as a selective barrier that regulates the
interaction of tissues with the environment. Polarity in epithelial cells
is generated by a series of molecular sorting events on the secretory and
endocytic pathways that ensure the specific transport of newly
synthesized, as well as internalized, membrane components to the
appropriate plasma membrane domain. Despite the fundamental importance of
these events, relatively little is known about the mechanisms by which
endosomes and the Golgi complex distinguish between components destined
for the apical and baolateral surfaces.
During the previous grant period, we found that the sorting of membrane
proteins in kidney epithelia, and probably other polarized cell types, is
controlled by a novel set of distinct but generally distributed
cytoplasmic domain determinants that specify transport to the basolateral
plasma membrane. These determinants are often dependent on critical
tyrosine or dileucine-containing motifs and thus bear some relationship
with signals that specify localization at clathrin-coated pits. We also
found that basolateral targeting determinants are dominant to, and
hierarchically arranged with, a second generally distributed signal that
specifies apical targeting: inactivation of the basolateral determinant
invariably results in transport to the apical plasma membrane. In
addition, the same basolateral signals are active in both the endocytic
and secretory pathways, suggesting that similar or identical sorting
strategies are used in both endosomes and the Golgi complex. Consequently,
it seems likely that the sorting mechanisms used by epithelial cells may
be widely conserved in different polarized cell types and throughout
evolution. We plan to make use of this information and extend our work to
elucidate the mechanism of polarized sorting at the cellular, biochemical,
and molecular levels. Our Specific Aims include: (1) Characterize the
structure, function, and distribution of basolateral sorting determinants;
(2) Identify factors that regulate polarized sorting in intact cells; (3)
Biochemically dissect the mechanism of sorting in endosomes through the
use of cell-free assays that reconstitute receptor sorting and transport
vesicle formation in vitro; (4) Identify and characterize cytosolic and/or
coat proteins likely to be involved in endosome (or Golgi) function; (5)
Characterize mammalian homologs of genes required for polarity during
budding in yeast.
许多哺乳动物细胞的质膜分化为
生化和功能上不同。这种不对称的安排
在上皮细胞的情况下,最好理解膜成分,
其表面两极化成顶端和基底外侧域
允许上皮用作调节的选择性障碍
组织与环境的相互作用。上皮细胞的极性
由分泌性的一系列分子分类事件产生
确保新运输的内吞途径
合成的以及内部化的膜成分
适当的质膜结构域。尽管至关重要
这些事件,关于该机制的知之甚少
内体和高尔基体综合体区分注定的组成部分
对于顶端和鲍尔外侧表面。
在上一个赠款期间,我们发现膜的排序
肾上皮中的蛋白质以及可能其他极化细胞类型的蛋白质是
由一组新颖但普遍分布的新颖的人控制
胞质结构域的决定因素,该决定因素指定运输到基底外侧
质膜。这些决定因素通常取决于关键
酪氨酸或含二李酮的基序,因此具有一定的关系
带有指定在网格蛋白涂层坑中定位的信号。我们也是
发现基底外侧靶向决定因素是主导的,并且
与层次结构一起排列,第二个通常分布的信号,
指定顶点靶向:基底外侧决定因素的灭活
总是会导致运输到顶端质膜。在
此外,相同的基底外侧信号在两个内吞作用中均处于活动状态
和分泌途径,表明相似或相同的排序
策略都用于内体和高尔基体综合体中。最后,
上皮细胞使用的分选机制似乎可能
在不同的极化细胞类型和整个范围内都广泛保守
进化。我们计划利用这些信息,并将我们的工作扩展到
阐明在生化的细胞上极化分选的机理
和分子水平。我们的具体目的包括:(1)表征
基底外侧分选决定簇的结构,功能和分布;
(2)确定调节完整细胞中极化分选的因素; (3)
从生化剖析内体中分选的机制
使用无细胞的测定,以重建受体分类和传输
体外形成囊泡; (4)识别和表征胞质和/或
外套蛋白可能参与内体(或高尔基体)功能; (5)
表征了极性所需基因的哺乳动物同源物
在酵母中萌芽。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

暂无数据
数据更新时间:2024-06-01
IRA S MELLMAN的其他基金
Research Programs-Immunology and Immunotherapy
研究项目-免疫学和免疫治疗
- 批准号:75132417513241
- 财政年份:2007
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
Cell Biology of the Immune Response
免疫反应的细胞生物学
- 批准号:65834936583493
- 财政年份:2003
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
CONTROL OF CELL POLARITY & PLASMA MEMBRANE FUNCTION BY RHO FAMILY GTPASE
电池极性的控制
- 批准号:65912566591256
- 财政年份:2002
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
CONTROL OF CELL POLARITY & PLASMA MEMBRANE FUNCTION BY RHO FAMILY GTPASE
电池极性的控制
- 批准号:65709366570936
- 财政年份:2002
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
CONTROL OF CELL POLARITY & PLASMA MEMBRANE FUNCTION BY RHO FAMILY GTPASE
电池极性的控制
- 批准号:65944116594411
- 财政年份:2002
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
CONTROL OF CELL POLARITY & PLASMA MEMBRANE FUNCTION BY RHO FAMILY GTPASE
电池极性的控制
- 批准号:65711556571155
- 财政年份:2002
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
CONTROL OF CELL POLARITY & PLASMA MEMBRANE FUNCTION BY RHO FAMILY GTPASE
电池极性的控制
- 批准号:64373786437378
- 财政年份:2001
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
CONTROL OF CELL POLARITY & PLASMA MEMBRANE FUNCTION BY RHO FAMILY GTPASE
电池极性的控制
- 批准号:64358286435828
- 财政年份:2001
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
CONTROL OF CELL POLARITY & PLASMA MEMBRANE FUNCTION BY RHO FAMILY GTPASE
电池极性的控制
- 批准号:64308496430849
- 财政年份:2001
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
相似国自然基金
结合眼动信息的弱监督显著实例分割及排序方法研究
- 批准号:62376238
- 批准年份:2023
- 资助金额:49 万元
- 项目类别:面上项目
基于网络上DARP的排序问题研究
- 批准号:12371317
- 批准年份:2023
- 资助金额:43.5 万元
- 项目类别:面上项目
图约束的排序及相关组合优化问题研究
- 批准号:12371316
- 批准年份:2023
- 资助金额:43.5 万元
- 项目类别:面上项目
绿色多目标在线排序问题研究
- 批准号:12371319
- 批准年份:2023
- 资助金额:43.5 万元
- 项目类别:面上项目
非支配排序遗传算法II的优化理论与算法研究
- 批准号:62306086
- 批准年份:2023
- 资助金额:30 万元
- 项目类别:青年科学基金项目
相似海外基金
Novel Inhibitors for Temporal Modulation of T-Lymphocytes during Chronic Heart Failure
慢性心力衰竭期间 T 淋巴细胞时间调节的新型抑制剂
- 批准号:1063834010638340
- 财政年份:2023
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
Defining the role of Wnt11 and Wnt5a in regulating hematopoietic and skeletal stem cell self-renewal potential during homeostasis and stress
定义 Wnt11 和 Wnt5a 在稳态和应激过程中调节造血和骨骼干细胞自我更新潜力的作用
- 批准号:1073165010731650
- 财政年份:2023
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
The role of BCL11B in T lineage fate during human thymopoiesis and pluripotent stem cell differentiation
BCL11B 在人类胸腺生成和多能干细胞分化过程中 T 谱系命运中的作用
- 批准号:1063937810639378
- 财政年份:2023
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
In utero exposure to alcohol-induced mammary stem cell deregulation and tumor risk later in life.
在子宫内暴露于酒精会导致乳腺干细胞失调和日后患肿瘤的风险。
- 批准号:1061884410618844
- 财政年份:2022
- 资助金额:$ 25.01万$ 25.01万
- 项目类别:
T cell diversity during chronic inflammation
慢性炎症期间 T 细胞多样性
- 批准号:1055860710558607
- 财政年份:2022
- 资助金额:$ 25.01万$ 25.01万
- 项目类别: