油酸盐通过通过S-化来调节膜微域动态来激活PLD2脂酶和GEF活性
Zhiqiang Guo1, Karl-Frédérik Bergeron1, Catherine Mounier1
1Biological Sciences Department, University of Quebec in Montréal (UQAM), Montréal, Quebec, Canada.
Journal of lipid research
|November 12, 2025
概括
油酸盐通过增强其S-化,改变其膜局部化,并通过Cdc42信号促进癌细胞迁移来激活脂酶D2 (PLD2).
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:
- 脂酶D2 (PLD2) 对细胞信号传递,膜动力学和癌症进展至关重要.
- 油酸盐 (OA) 激活PLD2,增强三阴性乳腺癌 (TNBC) 细胞迁移,但机制尚不清楚.
研究的目的:
- 阐明OA调节PLD2活动并促进TNBC细胞迁移的分子机制.
主要方法:
- 同焦点显微镜的共聚焦显微镜
- 脂质飞隔离器的隔离方法
- 进行S-化试验.
- 局部导向的突变发生.
主要成果:
- 氧化增强了PLD2在Cys223/Cys224的S-化,破坏了脂质的局部化,并增加了与PIP2微域的局部化.
- PLD2作为Cdc42的瓜核酸交换因子 (GEF),其活性由OA依赖的S-化和脂质动力学调节.
- 破坏S-化部位或脂质取消了PLD2-介导的Cdc42激活和细胞突起形成.
结论:
- 通过S-化和膜微域重组,OA调节PLD2活动.
- 这种机制为细胞迁移和信号传递中的PLD2调节提供了新的见解,特别是在TNBC中.
更多相关视频
相关概念视频
Lipids as Anchors
7.1K
In the plasma membrane, the lipids forming the bilayer can also act as an anchor to tether proteins to the membrane. The three main types of lipid anchors found in eukaryotes are – prenyl groups, fatty acyl groups, and glycosylphosphatidylinositol or GPI groups. Prenyl and fatty acyl groups act as anchors on the cytosolic surface of the membrane, whereas GPI anchors proteins on the extracellular side.
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
The carboxy-terminal of most of the prenylated proteins, such as Ras proteins, contains...
7.1K
Phosphoinositides and PIPs
10.0K
Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
10.0K
IP3/DAG Signaling Pathway
14.2K
Membrane lipids such as phosphatidylinositol (PI) are precursors for several membrane-bound and soluble second messengers. Specific kinases phosphorylate PI and produce phosphorylated inositol phospholipids. One such inositol phospholipids are the phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2], present in the inner half of the lipid bilayer. Upon ligand binding, GPCR stimulates Gq proteins to turn on phospholipase Cꞵ. Activated phospholipase Cꞵ cleaves PI(4,5)P2 and...
14.2K
Assembly of the Lipid Bilayer in the ER
4.0K
Biological membranes are more than just a barrier separating cell cytoplasm from the outside environment. They are highly dynamic and help maintain the integrity and physiological stability of the cells as well as membrane-bound organelles. Membranes also play vital roles in cell-to-cell and intracellular communication.
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
A large chunk of any biological membrane is composed of phospholipids. These lipids have a heterogeneous distribution across different subcellular organelles and even between...
4.0K
Biosynthesis of Lipids
508
Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
508
Asymmetric Lipid Bilayer
9.5K
Biological membranes show uneven distribution of different types of lipids in the inner and outer layers, resulting in transverse asymmetric membranes. The treatment of the erythrocyte membrane with the enzyme phospholipase confirmed the asymmetric nature of the lipid bilayer. The enzyme hydrolyzes lipids into fatty acids and hydrophilic groups. The phospholipase acts only on the outer layer of the membrane, while the inner layer remains intact. The phospholipase treatment resulted in 80%...
9.5K


