克拉斯通过空间循环的溶解,捕获和囊泡运输定位到等离子体膜
Malte Schmick1, Nachiket Vartak1, Björn Papke1
1Department of Systemic Cell Biology, Max Planck Institute for Molecular Physiology, Otto-Hahn-Straße 11, 44227 Dortmund, Germany.
Cell
|April 15, 2014
概括
在血上KRas蛋白质的丰富依赖于一种新型的反应-扩散循环,涉及PDEδ和Arl2,而不仅仅是静电相互作用. 这说明了针对PDEδ如何影响KR的空间组织和信号.
科学领域:
- 细胞生物学 细胞生物学
- 分子瘤学分子瘤学
- 生物物理学的生物物理.
背景情况:
- KRas信号传递对细胞生长至关重要,并依赖于血膜 (PM) 丰富.
- KRas的PM局部化涉及与脂的前化和静电相互作用.
- 现有的模型无法完全解释由于内膜表面积而导致的KRas PM丰富.
研究的目的:
- 为了研究控制KRas活细胞动态的动力学参数.
- 阐明了超越静电相互作用的KRas PM丰富的机制.
- 了解如何准KRas调节器影响其空间组织.
主要方法:
- 利用基于蜂自动机的数据拟合方法来测量KR的动力参数.
- 在现实的细胞几何学中分析了KRas的动态.
- 研究了细胞质化酶三角酶 (PDEδ) 和Arf样蛋白2 (Arl2) 在KRas局部化中的作用.
主要成果:
- 仅仅是静电相互作用对于KRas的PM丰富是不够的.
- 细胞质PDEδ连接剂将KRas从内膜中错位.
- 在Arl2-依赖的向周核膜的卸载和随后在回收内体 (RE) 的捕获之前,PM通过膀运输恢复.
- 一个涉及PDEδ和Arl2的反应-扩散循环驱动KR的空间组织.
结论:
- 克拉斯的颗粒丰富是通过能量驱动的反应-扩散循环维持的,而不仅仅是静电.
- 这一循环涉及连续的绑定和释放,由PDEδ和Arl2.2介导.
- 针对PDEδ的小分子破坏了KR的空间组织,提供了治疗潜力.
相关概念视频
Clathrin Coated Vesicles
8.1K
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...
8.1K
ER Retrieval Pathway
3.8K
In the secretory pathway, vesicles transport proteins from one cellular compartment to another in forward transport to deliver the protein to its correct location. Occasionally, misfolded proteins and incorrect proteins escape their original compartments, and a retrieval pathway is used to return the escaped proteins to their original compartment.
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
The ER uses many checkpoints to prevent the entry of incorrectly folded or a resident protein as cargo onto a transport vesicle. These mechanisms...
3.8K
Rab Cascades
2.8K
Rab GTPases act in a regulated cascade during membrane fusion, helping the lipid bilayers mix. The Rab family of proteins are active when bound to GTP, and inactive when bound to GDP. Hence, they act as guanine nucleotide-dependent molecular switches. Rab-GTP recognizes and binds to long or short-range tethering proteins to capture the target vesicle. These tethers coordinate with SNAREs on the vesicle and the target membrane to assemble the trans SNARE complex that locks the mixing bilayers.
2.8K
Recycling Endosomes and Transcytosis
2.8K
The recycling endosome, also known as the endosomal recycling compartment (ERC), is a part of the slow-recycling process of the endocytic pathway. Molecules internalized through receptor-mediated endocytosis are either degraded in the lysosomes or are recycled to the plasma membrane through the fast- or slow-recycling route.
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
The recycling endosome is not a single organelle but an extensively tubulated network of recycling pathways. It functions in storing molecules or transporting them across...
2.8K
Overview of Protein Sorting and Transport
17.1K
Eukaryotic cells have different membrane-bound organelles with distinct protein requirements. The process by which proteins are targeted to a specific organelle is called protein sorting.
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...
Protein sorting can be of two types: signal-based sorting and vesicle-based trafficking. In signal-based sorting, specific amino acid sequences called sorting signals target proteins to the proper location inside the cell either via gated transport or by protein translocation. In gated transport, folded...
17.1K
Vesicular Tubular Clusters
2.4K
After budding out from the ER membrane, some COPII vesicles lose their coat and fuse with one another to form larger vesicles and interconnected tubules called vesicular tubular clusters or VTCs. These clusters constitute a compartment at the ER-Golgi interface known as ERGIC (Endoplasmic Reticulum Golgi Intermediate Compartment). The ERGIC is a mobile membrane-bound cargo transport system that sorts proteins secreted from ER and delivers them to the Golgi.
With the help of motor proteins such...
With the help of motor proteins such...
2.4K


