证据表明,在神经元体膜区内,APP内部化存在一个与克拉林无关的内细胞通路
Jonathan Aow1, Tzu-Rung Huang2, Yeek Teck Goh3
1Genome Institute of Singapore, Agency for Science, Technology and Research (A(∗)STAR), 60 Biopolis Street, Genome, Singapore 138672, Singapore; Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
Cell reports
|July 14, 2023
概括
在神经元中内化索马托登德里特粉样蛋白前体蛋白 (APP) 绕过了依赖克拉的通路. 这表明,内化APP可能不是氨基酸β (Aβ) 生产的主要来源.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 粉样蛋白前体蛋白 (APP) 通过克拉/动氨酸介导的内细胞分裂 (CME) 的内化与粉样β (Aβ) 生产有关.
- 据认为,APP上的YENPTY图案调解了这种CME通路.
研究的目的:
- 为了研究神经元中体膜APP内部化的机制.
- 确定APP内部化在Aβ生产中的作用.
主要方法:
- 利用初级动物神经元和诱导人类神经元.
- 抑制了动氨酸并突变了APP YENPTY动机.
- 评估了APP内部化,回收,降解和Aβ分泌.
主要成果:
- 神经元中的体腺体APP内化是dynamin-和YENPTY-独立的,表明一个克拉素-独立的途径.
- APP YENPTY突变或胺抑制减少分泌的Aβ.
- 低密度脂蛋白受体 (LDLR) 也使用一种CME独立的途径.
结论:
- 与非神经细胞相比,神经细胞APP内部化使用不同的途径.
- 内部化的体内膜 APP 可能不是 Aβ 生产的主要贡献者.
- 神经内细胞路径显著不同,影响Aβ分泌机制.
相关概念视频
Clathrin Coated Vesicles
7.1K
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...
7.1K
Receptor-mediated Endocytosis
6.2K
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...
6.2K
Delivery Pathways to the Lysosome
6.6K
Eukaryotic cells use different mechanisms to eliminate toxic waste obsolete and worn-out substances. Lysosomes play a pivotal role in this, and hence, these substances are carried to the lysosome from other parts of the cell and extracellular space through different pathways. The most elaborately studied pathways to the lysosome are the endocytic pathways.
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
Endocytosis
In endocytosis, the cell membrane takes up macromolecules and particles from the surrounding medium. Clathrin-mediated...
6.6K
ER Retrieval Pathway
3.9K
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...
3.9K
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
Fusion of Secretory Vesicles with the Plasma Membrane
11.1K
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
11.1K


