棕酸转移酶控制DNAJC5的膜定位,以调节非传统的蛋白质分泌
Yue Xu1, Robbins Puthenveetil2, Juhyung Lee1
1Laboratory of Molecular Biology, National Institute of Diabetes, Digestive, and Kidney Diseases, Bethesda, Maryland, USA.
Traffic (Copenhagen, Denmark)
|February 9, 2026
概括
错误折叠蛋白质分泌 (MAPS) 涉及DNAJC5,一种可以被棕化蛋白质的蛋白质. DHHC11对DNAJC5的棕化增强了其戈尔吉关联,并驱动了非常规的蛋白质分泌.
科学领域:
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
- 生物化学 生化学
背景情况:
- 非传统蛋白质分泌 (UcPS) 允许细胞分泌缺乏信号序列的蛋白质.
- 错误折叠相关蛋白质分泌 (MAPS) 是一个UcPS途径,涉及HSP70和DNAJC5.5.
- 在MAPS中,DNAJC5是与HSP70相关的辅导员.
研究的目的:
- 调查DNAJC5在MAPS中的翻译后修改的作用.
- 确定负责DNAJC5修饰的酶及其对分泌的影响.
- 确定DNAJC5的特定区域,这些区域对其定位和分泌至关重要.
主要方法:
- 人类细胞培养和转染.
- 使用DHHC酶对蛋白质棕化酶的分析.
- 突变性研究以确定DNAJC5.5的功能域.
- 同焦显微镜评估亚细胞局部化 (戈尔吉协会).
- 测量蛋白质分泌水平的测量.
主要成果:
- 在人类细胞中,DNAJC5被多个DHHC棕酸转移酶棕化.
- DHHC11的过度表达导致DNAJC5的戈尔吉丰富和分泌量的增加.
- 含有囊氨酸链域的最小DNAJC5模块 (DC95) 足以进行棕化,戈尔吉转位和分泌.
- 氨酸链域内或周围的特定残留物对于这些过程至关重要.
结论:
- 棕化是MAPS中DNAJC5功能的关键调节机制.
- 棕化位点和相邻的序列决定了DNAJC5的亚细胞定位及其在UcPS中的作用.
- 这项研究阐明了一种新的调节机制,控制了错误折叠的蛋白质的非传统分泌.
更多相关视频
08:00Spatiotemporal Control of Protein Activity through Optogenetic Allosteric Regulation
Published on: October 4, 2024
1.1K
10:41Confocal and Super-Resolution Imaging of Polarized Intracellular Trafficking and Secretion of Basement Membrane Proteins During Drosophila Oogenesis
Published on: May 19, 2022
2.6K
相关概念视频
Regulation of Hormone Secretion
6.9K
Regulation of hormone secretion is a finely tuned orchestration driven by various types of stimuli, encompassing neural, humoral, and hormonal signals. Environmental cues instigate neural stimuli, where action potentials traverse nerve fibers to reach their designated targets. An illustrative scenario is the body's response to stress, wherein the sympathetic nervous system releases epinephrine from the adrenal glands, inducing the well-known 'fight or flight' reaction.
Humoral...
Humoral...
6.9K
Regulated Protein Degradation
8.9K
It is vital to regulate the activity of enzymatic as well as non-enzymatic proteins inside the cell. This can be achieved either through creating a balance between their rate of synthesis and degradation or regulating the intrinsic activity of the protein. Both these regulation mechanisms play an essential role in the normal functioning of cells.
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
Protein degradation plays two important roles in the cells. It helps to protect cells from misfolded or damaged proteins before they lead to a...
8.9K
Regulated Protein Degradation
3.2K
3.2K
Covalently Linked Protein Regulators
9.7K
Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....
These groups modify specific amino acids in a protein....
9.7K
Introduction to Membrane Proteins
81.4K
The cell membrane, or plasma membrane, is an ever-changing landscape. It is described as a fluid mosaic where various macromolecules are embedded in the phospholipid bilayer. Among the macromolecules are proteins. The protein content varies across cell types. For example, mitochondrial inner membranes contain ~76% protein content, while myelin contains ~18% protein content. Individual cells contain many types of membrane proteins—red blood cells contain over 50—and different cell...
81.4K
Regulated mRNA Transport
7.0K
In eukaryotes, transcription and translation are compartmentalized; an mRNA is first synthesized in the nucleus and then selectively transported to the cytoplasm for protein synthesis. Before transport, a pre-mRNA undergoes several steps of post-transcriptional modifications including splicing, 5' capping, and the addition of a poly-adenine tail. Various proteins bind to the pre-mRNA during these modifications. The mRNA transport takes place with the help of multiple proteins playing...
7.0K
