Lysosome 表面是 Vasopressin V2 受体信号传递的一个不知名的中心
bioRxiv : the preprint server for biology
|November 19, 2025
概括
G蛋白结合受体 (GPCRs) 从 lysosomal 表面发出信号. 血管压素V2受体 (V2R) 在降解之前激活 lysosomes 的 G 蛋白和 β-arrestins.
科学领域:
- 细胞生物学 细胞生物学
- 分子药理学分子药理学
- 信号传输 信号传输
背景情况:
- 传统上,G蛋白结合受体 (GPCR) 从细胞表面发出信号.
- 新出现的证据表明,GPCRs可以从细胞内细胞器官发出信号.
- 血管压素V2受体 (V2R) 从内分泌体内化并发出信号,在溶解体中进行潜在信号传递.
研究的目的:
- 为了检查静脉压素V2受体 (V2R) 是否从 lysosomal 表面发出信号.
- 在细胞内实时跟踪V2R贩运和传感器激活.
主要方法:
- 使用NanoBiT旁观者方法实时跟踪V2R贩运和传感器激活.
- 采用纳米体/体内生物传感器来评估内源G蛋白和β-arrestin的激活.
- 抑制V2R转移到内解体区,以评估其对信号传输的影响.
主要成果:
- 激活的V2R迅速传输到 lysosomes,保持其与G蛋白和β-arrestins配对的能力.
- 在 lysosomal 表面,V2R 激活了内源的 G 蛋白和 β 止蛋白.
- 抑制V2R运动到内分泌体减少了G蛋白信号传递.
结论:
- 溶解体表面作为某些GPCR的信号枢纽,包括V2R.
- 在受体降解之前,V2R信号发生在 lysosomal 膜上.
- 这一发现扩大了对GPCR信号位置和机制的理解.
相关概念视频
Clathrin Coated Vesicles
9.0K
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...
9.0K
Receptor-mediated Endocytosis
110.4K
Overview
110.4K
Receptor-mediated Endocytosis
7.5K
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...
7.5K
Overview of Secretory Vesicles
9.3K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
9.3K
Receptor Downregulation in MVBs
2.7K
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...
2.7K
Endocrine Signaling
67.7K
Endocrine cells produce hormones to communicate with remote target cells found in other organs. The hormone reaches these distant areas using the circulatory system. This exposes the whole organism to the hormone but only those cells expressing hormone receptors or target cells are affected. Thus, endocrine signaling induces slow responses from its target cells but these effects also last longer.
67.7K


