GGA1与内体Na+/H+交换器NHE6相互作用,控制到内体区的局部化
bioRxiv : the preprint server for biology
|November 21, 2023
概括
研究人员发现,Golgi相关蛋白GGA1与内体内Na+/H+交换器NHE6.6相互作用. 这种相互作用对于正确地将NHE6定位到内分泌体至关重要,影响神经元功能和克里斯蒂安森综合征.
科学领域:
- 细胞生物学 细胞生物学
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 在Na+/H+交换器6 (NHE6) 中的突变导致克里斯蒂安森综合征,一种神经疾病.
- 在神经元中,NHE6对于内体酸化和成熟至关重要.
研究的目的:
- 为了确定与NHE6.6相互作用的蛋白质.
- 阐明NHE6相互作用蛋白在NHE6局部化和神经元功能中的功能性作用.
主要方法:
- 酵母两种混合选,以确定交互的合作伙伴.
- 共同免疫沉 (co-IP) 来确认相互作用.
- 超高分辨率显微镜可视化共定位.
- 亚细胞分离以评估淘汰细胞中的蛋白质局部化.
主要成果:
- 与戈尔吉相关的,含有玛适配素的ARF结合蛋白1 (GGA1) 被确定为NHE6相互作用体.
- NHE6和GGA1在海马神经元中同定位.
- GGA1的损失导致NHE6从内分体到 lysosomes和Golgi的错误定位,化Golgi的光pH.
结论:
- NHE6和GGA1之间的相互作用对于NHE6正确地定位到内分泌体至关重要.
- 这种相互作用的破坏有助于在克里斯蒂安森综合征中观察到的细胞缺陷.
相关概念视频
Rab Cascades
2.7K
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.
2.7K
Directionality of Nuclear Transport
3.3K
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...
3.3K
The Early Endosome: Endocytosis of Transferrin
3.3K
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...
3.3K
Nuclear Protein Sorting
4.6K
Nuclear protein sorting is the selective trafficking of histones, polymerases, gene regulatory proteins into the nucleus and exporting RNAs and ribosomes to the cytosol. It is a tightly controlled process that regulates gene expression within a cell.
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
Proteins targeted to the nucleus carry nuclear localization signals or NLS recognized by import receptors in the cytosol. Similarly, proteins with nuclear export signals are recognized by export receptors. Import and export receptors are...
4.6K
Nuclear Export
3.7K
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...
3.7K
Rab Proteins
3.9K
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...
3.9K


