lysosomal 进入的一个机制
Matthew Zajac1,2, Sourajit Mukherjee1,2, Palapuravan Anees1,2
1Department of Chemistry, The University of Chicago, Chicago, IL 60637, USA.
Science advances
|February 14, 2024
概括
科学家们发现了一种新基因,虫中的LCI-1及其人类版本TMEM165,它将导入溶酶体. 这一发现为溶解体调节和神经退行性疾病的潜在治疗标提供了新的见解.
科学领域:
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 溶解体释放的对于细胞信号传递至关重要.
- 溶解体补充其储量的机制仍然是未知的.
- 溶解体失调与神经退行性疾病有关.
研究的目的:
- 为了识别参与溶解体平衡的基因.
- 为了阐明 lysosomal 补充的机制.
- 探索溶酶体储存障碍的潜在治疗点.
主要方法:
- 在 *Caenorhabditis elegans* 中进行RNA干扰选.
- 鉴定出基因及其人类同类 (TMEM165) 的功能性特征.
- 两个离子映射和电生理学.
主要成果:
- 一个进化保守的基因,lci-1*,被确定为溶解体进入的促进者.
- 人类同类物,TMEM165 (人体LCI),作为一个质子激活的溶酶体进口器.
- TMEM165以pH取决的方式将引入溶酶体.
结论:
- 人类LCI的发现 (TMEM165) 提供了对溶酶体进口者的第一个描述.
- 这一发现为了解溶解体通道生理学开辟了新的途径.
- 向溶酶体进口可能为神经退行性疾病提供新的治疗策略.
相关概念视频
Feedback Regulation of Calcium Concentration
3.4K
Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
3.4K
Lysosomes
17.9K
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,...
17.9K
Lysosomal Hydrolases
3.8K
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,...
3.8K
Overview of Secretory Vesicles
8.5K
Secretory vesicles, also known as dense core vesicles (DCVs), are membrane-bound vesicles that transport secretory proteins, such as hormones or neurotransmitters. Regulated secretory vesicles transport proteins from the trans-Golgi network to the exterior of the cell. Proteins present in regulated secretory vesicles are required to be rapidly exocytosed in large amounts upon a specific stimulus.
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
Various proteins regulate the aggregation of molecules inside the secretory vesicles. Chromogranins...
8.5K
Delivery Pathways to the Lysosome
6.5K
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...
6.5K
Calmodulin-dependent Signaling
5.1K
Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
5.1K


