增长因子受体系统的空间和信号重叠在克拉林涂层的部位
Marco A Alfonzo-Méndez1, Marie-Paule Strub1, Justin W Taraska1
1Biochemistry and Biophysics Center, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD 20892.
Molecular biology of the cell
|September 18, 2024
概括
细胞通信依赖于等离子体膜蛋白质复合体. 增长因子刺激揭示了不同的蛋白质特征,以及在克拉林涂层部位的受体和调节因子的协集,整合了信号通路.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 细胞通信对于多细胞生物来说至关重要.
- 等离子膜蛋白质复合体调节细胞对外部线索的反应.
- 这些复合物的精确组成和调节仍然不完全理解.
研究的目的:
- 为了研究等离子体膜上的克拉涂层结构的蛋白质组成和动态.
- 为了映射生长因子受体和相关蛋白质的局部化,以应对刺激.
- 阐明受体协集群和激活的机制.
主要方法:
- 高分辨率和高通量光成像人类状细胞HSC3.
- 在单个克拉特林涂层结构中分析蛋白质定位.
- 药理学上对受体活动的干扰.
主要成果:
- 在对照细胞和生长因子刺激细胞之间观察到不同的蛋白质特征.
- 皮表皮生长因子 (EGF) 刺激诱导了EGFR,FGFR1和LDLR的招募到克拉思林涂层部位.
- 包括Cbl,Grb2和dynamin2在内的调节蛋白也被招募,受体活动中断阻止了协集.
- 刺激EGF导致FGFR1酸化,表明交叉激活.
结论:
- 在刺激时,在克拉斯林涂层部位发生新的共同聚类和生长因子受体和调节因子的激活.
- 这个过程集成了等离子体膜上的生长因子信号通路.
- 这些发现提供了对细胞外线和药理学剂的复杂细胞反应的见解.
相关概念视频
Assembly of Signaling Complexes
5.7K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.7K
Intracellular Signaling Affects Focal Adhesions
2.6K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.6K
Clathrin Coated Vesicles
6.9K
Clathrin-coated vesicles use endocytosis to transport receptors and lysosomal hydrolases from the Golgi to the lysosome in the late secretory pathway. Clathrin-mediated endocytosis was the first described endocytic process, and Clathrin-coated vesicles remain one of the most well-studied transport vesicles. The molecular machinery that generates clathrin-coated vesicles comprises over 50 proteins that precisely coordinate vesicle formation. Cell surface receptors concentrated in indented sites...
6.9K
Receptor Downregulation in MVBs
2.0K
Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
2.0K
Receptor-mediated Endocytosis
6.0K
Receptor-mediated endocytosis is when bulk amounts of specific molecules are imported into a cell after binding to cell surface receptors. The molecules bound to these receptors are taken into the cell through inward folding of the cell surface membrane, which is eventually pinched off into a vesicle within the cell. Structural proteins, such as clathrin, coat the budding vesicle.
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
Clathrin-Mediated Endocytosis of LDL
One well-characterized example of receptor-mediated endocytosis is the...
6.0K
Amplifying Signals via Second Messengers
6.8K
Many receptor binding ligands are hydrophilic; they do not cross the cell membrane but bind to cell-surface receptors. Thus, their message must be relayed by second messengers present in the cell cytoplasm. There are several second messenger pathways, each with its own way of relaying information. For example, the G protein-coupled receptors can activate both phosphoinositol and cyclic AMP (cAMP) second messenger pathways. The phosphoinositol pathway is active when the receptor induces...
6.8K


