相关实验视频

Updated: Sep 13, 2025

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking

The Microscopy-Based Assay to Study and Analyze the Recycling Endosomes using SNARE Trafficking

Published on: February 12, 2022

NCAM2促进了从细胞表面到含有BACE1的循环内分体的APP向

Grant Pfundstein¹, Ryan Keable¹, Shangfeng Hu¹

¹School of Biotechnology and Biomolecular Sciences, The University of New South Wales, Sydney, New South Wales 2052, Australia.

Progress in neurobiology

|July 28, 2025

概括

神经细胞粘附分子2 (NCAM2) 与粉样蛋白前体蛋白 (APP) 结合,促进其与内体中BACE1的融合. 这种相互作用促进了粉样β (Aβ) 生产,这是阿尔茨海默氏症的关键因素.

科学领域:

神经科学是一个神经科学.
分子生物学分子生物学
细胞生物学细胞生物学

背景情况:

阿尔茨海默氏病 (AD) 的发病包括粉样蛋白前体蛋白 (APP) 和BACE1在内分体中的融合,产生粉样β (Aβ) .
驱动神经元中APP和BACE1融合的机制尚不清楚,这阻碍了治疗策略.
神经细胞粘附分子2 (NCAM2) 参与增加Aβ水平,但其确切作用尚不清楚.

研究的目的:

阐明NCAM2影响APP处理和Aβ生产的机制.
为了研究NCAM2,APP和BACE1在神经元路径中的相互作用.

主要方法:

通过生物化学分析,研究了APP与NCAM2的结合.
利用细胞培养模型 (CHO细胞和神经元) 研究APP贩运和BACE1分裂.
研究了NCAM2表达和缺陷对APP局部化和Aβ产生的影响.
评估了Aβ寡合体和神经元活动对NCAM2-APP结合的影响.

主要成果:

NCAM2直接与APP的细胞外域结合;其细胞内域与Rab11-FIP5.5相互作用.
NCAM2促进了APP/NCAM2复合体的内细胞分裂,并将其向含有BACE1.1的Rab11阳性循环内体.
NCAM2表达增强了APP与BACE1的融合,增加了氨基原性APP裂变产物和Aβ水平.
NCAM2 缺乏导致 APP 在细胞表面积累,并在循环内分泌体中降低水平.
Aβ寡聚体和NMDA受体激活增强NCAM2-APP的结合,进一步增加Aβ的产生.

结论:

NCAM2充当一个关键的调解者,结合APP并将其引导到循环内分体,用于BACE1裂变.
这种新型的NCAM2-依赖性途径有助于APP/BACE1的融合和随后的阿尔茨海默病中的Aβ积累.
准NCAM2-APP相互作用是一个潜在的治疗策略,可以减少AD中的Aβ产生.

关键词:

粉样蛋白β是什么粉样蛋白β是什么粉样蛋白前体蛋白是一种前体蛋白.在BACE1中获得了BACE1学位.内分泌体内分泌体内分泌体内分泌体内分泌体内分泌体内分泌体内分泌体内分泌体神经细胞粘附分子 2 2 神经细胞粘附分子拉伯11 拉伯11 拉伯11 拉伯11 拉伯11 拉伯11 人口贩运人口贩运

更多相关视频

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells

Analysis of Endocytic Uptake and Retrograde Transport to the Trans-Golgi Network Using Functionalized Nanobodies in Cultured Cells

Published on: February 21, 2019

The Cell-based L-Glutathione Protection Assays to Study Endocytosis and Recycling of Plasma Membrane Proteins

The Cell-based L-Glutathione Protection Assays to Study Endocytosis and Recycling of Plasma Membrane Proteins

Published on: December 13, 2013

相关概念视频

Recycling Endosomes and Transcytosis

Recycling Endosomes and Transcytosis

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...

ER Retrieval Pathway

ER Retrieval Pathway

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...

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like Cell Adhesion Molecules

Immunoglobulin-like cell adhesion molecules or Ig-CAMs are a versatile group of cell surface glycoproteins belonging to the immunoglobulin protein superfamily. Ig-CAMs possess the characteristic immunoglobulin protein domains and other domains such as the fibronectin type III domain. The Ig domains are glycosylated to varying degrees in different Ig-CAMs.
Ig-CAMs exhibit either homophilic binding (to other Ig-CAMs) or heterophilic binding (to other ligands such as integrins). While most Ig-CAMs...

Receptor-mediated Endocytosis

Receptor-mediated Endocytosis

Clathrin Coated Vesicles

Clathrin Coated Vesicles

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...

Rab Cascades

Rab Cascades

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.