血到溶酶体的FGR信号调节了与内细胞结合相关的溶酶体平衡
Qiuyuan Yin1,2, Jifan Qian1, Xiao Ding3
1Center for Life Sciences, School of Life Sciences, Yunnan University , Kunming, China.
The Journal of cell biology
|January 6, 2026
概括
新的研究确定了SRC-1/-2和FGR激酶是溶解体生物发生的关键调节者. 这些蛋白质通过从细胞表面向溶解体发送信号来控制溶解体数量,从而影响细胞对压力的适应.
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:
- lysosome生物发生的转录控制对于细胞适应压力至关重要.
- 将细胞表面信号与 lysosome 数量变化的联系机制尚不清楚.
研究的目的:
- 为了确定 lysosome生物发生的新型调节者.
- 阐明连接细胞表面事件与溶酶体形成的信号通路.
主要方法:
- 开发了一个基于Caenorhabditis elegans的异质TFE3激活系统.
- 在C. elegans和哺乳动物细胞中利用了基因失活 (src-1/-2) 和药理抑制 (FGR).
- 使用内分细胞和溶酶体路径分析研究了蛋白质局部化和相互作用.
主要成果:
- 确定了非受体铁激酶SRC-1/-2 (C. elegans) 和FGR (哺乳动物) 作为关键调节剂.
- src-1/-2 失活或FGR 抑制/缺陷导致了TFEB/TFE3依赖的溶酶体增加.
- FGR 激酶激活AKT2,并通过内细胞分裂被运送到溶酶体,在那里它抑制TFEB/TFE3酸化.
结论:
- 发现了一种新型的血到溶酶体信号轴,调节了溶酶体平衡.
- 这一途径对于适应 lysosome biogenesis 作为对内细胞分裂的反应至关重要.
- SRC-1/-2和FGR激酶代表了与压力相关的细胞适应的潜在治疗点.
相关概念视频
01:36Delivery Pathways to the Lysosome
8.7K
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...
8.7K
00:58Recycling Endosomes and Transcytosis
3.5K
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...
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...
3.5K
01:31Lysosomes
25.3K
Lysosomes are membrane-enclosed spherical sacs derived from the Golgi apparatus. The most important function of the lysosome is degrading macromolecules and biological polymers that are released during membrane trafficking events such as the secretory, endocytic, autophagic, and phagocytic pathways. The degradation is carried out by several hydrolytic enzymes active in an acidic environment of the lysosomal lumen. These acid hydrolases are involved in cellular processes such as cell signaling,...
25.3K
01:15Receptor Downregulation in MVBs
2.8K
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...
2.8K
01:22Lysosomal Hydrolases
4.4K
Lysosomes are the site for the degradation of macromolecules and biological polymers released during membrane trafficking events such as secretory, endocytic, autophagic, and phagocytic pathways. The membrane-enclosed area of the lysosome, called the lumen, contains hydrolytic enzymes active in an acidic environment. These acid hydrolases are functional at a pH between 4.5 and 5 and are involved in cellular processes such as cell signaling, energy metabolism, restoration of the plasma membrane,...
4.4K
01:28The Early Endosome: Endocytosis of Transferrin
4.7K
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...
4.7K