质子交换器NHE9 pHine通过损害Rab7活动来调整外体细胞的产生
Mariam Duhaini1, Perla Fares1, Lili Hafezi1
1Department of Natural Sciences, University of Michigan-Dearborn, Dearborn, Michigan, USA.
The Journal of biological chemistry
|February 5, 2025
概括
和质子交换器NHE9调节内体的pH值,影响外体的产生. 通过NHE9介导的化破坏了 lysosomal 的传递,但增强了 exosome 的分泌.
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 生物化学
背景情况:
- 外体细胞通过运送生物活性分子来调解细胞间的通信.
- 外体生物发生在内细胞路径中,受内体 pH 的影响.
- 连接内体pH与外体生产的精确分子机制尚未完全理解.
研究的目的:
- 调查和质子交换器NHE9在调节内体pH和外体生产中的作用.
- 阐明内体pH影响外体生物发生和分泌的分子机制.
主要方法:
- 用基因工程来操纵NHE9的功能.
- 生物化学测试用于评估分子相互作用和途径.
- 先进的显微镜可视化内体的动态和外体分泌.
主要成果:
- 通过调节内体pH值,NHE9活动显著影响外体的产生.
- 通过NHE9介导的内体化会损害Rab7的激活和溶酶体向.
- 光性化促进了Rab27b的招募,增强了外体的分泌.
结论:
- 内体pH值是外体细胞生产的关键调节者.
- NHE9在控制内体pH方面发挥着关键作用,从而影响外体生物发生和释放.
- NHE9代表了调节外体组动态的潜在治疗标.
相关概念视频
Rab Cascades
2.6K
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.
2.6K
Rab Proteins
3.8K
Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.8K
Nuclear Export
3.6K
The nucleus restricts several proteins within and allows others to pass. The restricted proteins possess a nuclear retention sequence or NRS, anchoring them to the nuclear lamins and preventing their transport to the cytosol. The non-restricted proteins, after their synthesis, are transported to their site of action, such as the cytosol or other organelles, with the help of nuclear export signals or NES.
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
NES are of three types- the canonical 10-residue long leucine-rich signal and other...
3.6K
The Early Endosome: Endocytosis of Transferrin
3.2K
Essential proteins such as insulin or low-density lipoprotein (LDL) and micronutrients such as iron enter a eukaryotic cell through receptor-mediated endocytosis. Subsequently, the early endosomes fuse with the vesicles containing such receptor-ligand complexes and play a vital role in sorting the incoming ligands and receptors. While the ligands are either degraded inside the vesicle or released into the cytosol, their receptors are returned to the plasma membrane for further rounds of...
3.2K
Regulation of Nuclear Protein Sorting
2.4K
Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
Directionality of Nuclear Transport
3.2K
Ras-related nuclear protein or Ran is a small G protein that cycles between its GTP and GDP bound states. Ran specific regulators, a Ran GTPase Activating Protein or RanGAP present in the cytosol and a Ran guanine nucleotide exchange factor or RanGEF present inside the nucleus regulate GTP/GDP exchange. A high concentration of GTP inside the cells, in addition to this asymmetric distribution of Ran-specific regulators, leads to a higher RanGTP concentration inside the nucleus. This...
3.2K


