突触胺1的柔膜连接器通过液-液相分离来调节Ca2+的结合
Nikunj Mehta1, Sayantan Mondal2, Emma T Watson1
1Howard Hughes Medical Institute, Department of Neuroscience, University of Wisconsin-Madison, Madison, WI, 53705, USA.
Nature communications
|January 4, 2024
概括
赛纳普托塔格明-1 (Syt1) 使用其柔膜链接器形成液体液相分离 (LLPS) 凝结物. 这种自我关联调节Syt1.
科学领域:
- 分子神经科学 分子神经科学
- 细胞生物学 细胞生物学
- 生物物理学的生物物理.
背景情况:
- синапто塔格敏-1 (Syt1) 是一个关键的 Ca2+ 传感器,用于突触囊泡外细胞形成.
- 在体内,Syt1充当多元体,利用并列的C2域来感知Ca2+.
- 蛋白质通过单个跨膜域与膜结,通过一个柔膜链接器连接.
研究的目的:
- 研究Syt1柔膜链接器在蛋白质功能中的作用.
- 为了确定链接器是否介导液-液相分离 (LLPS).
- 阐明LLPS如何影响Syt1的Ca2+敏感性和外细胞形成调节.
主要方法:
- 生物化学测试以描述柔膜链接区域的特征.
- 在体外和体内实验观察LLPS和凝结物形成.
- 在存在Syt1凝结物时测量Ca2+灵敏度和聚变动态.
主要成果:
- 该Syt1柔膜链接器包含一个氨酸丰富,内在无序的区域.
- 这一区域对于调解Syt1液态液相分离 (LLPS) 是必要且足够的.
- 凝结物形成负面调节Syt1的Ca2+敏感性,而Ca2+和离子脂促进相位分离.
- 增加的细胞内Ca2+促进活细胞中Syt1滴的融合.
结论:
- 通过LLPS,Syt1的柔膜链接器通过LLPS作为其功能的调节器.
- LLPS创建了一个凝结物介导的反循环,微调Ca2+触发的外细胞形成.
- 通过LLPS的Syt1自我结合会影响Ca2+结合和融合过程中的膜曲率.
更多相关视频
12:01Acute Dissociation of Lamprey Reticulospinal Axons to Enable Recording from the Release Face Membrane of Individual Functional Presynaptic Terminals
Published on: October 1, 2014
8.9K
08:15Membrane Remodeling of Giant Vesicles in Response to Localized Calcium Ion Gradients
Published on: July 16, 2018
8.0K
相关概念视频
01:16Calmodulin-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
01:33Overview 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
01:26Fusion of Secretory Vesicles with the Plasma Membrane
11.1K
Proteins and neurotransmitters in secretory vesicles can be released from a cell upon vesicle docking, priming, and fusion with the plasma membrane. Vesicles are docked and primed in preparation for the quick exocytosis of their contents in response to a stimulus. The fusion process is mainly carried out by a SNAP Receptor or SNARE complex, consisting of synaptobrevin, syntaxin-1, and SNAP-25.
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
In 1993, Jim Rothman proposed that the antiparallel pairing of vesicular and transmembrane SNAREs, or...
11.1K
01:27Feedback 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
01:43SNAREs and Membrane Fusion
10.9K
Once a transport vesicle has recognized its target organelle, the vesicular membrane needs to fuse with the target membrane to unload the cargo. Transmembrane proteins called SNAREs present on organelle membranes and their vesicles, mediate vesicle fusion.
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
SNAREs exist in pairs that symmetrically interact and catalyze the fusion of the lipid bilayers in vesicle and target organelle. v-SNARE in the vesicle membrane are single polypeptide chains that bind to a complementary t-SNARE, composed of 2...
10.9K
01:19Membrane Asymmetry Regulating Transporters
4.5K
Enzymes like flippase, floppase, and scramblase transfer phospholipids from one layer to another in the membrane, thereby affecting membrane asymmetry.
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
Flippase
Eukaryotic flippases are type-IV P-type ATPases or P4-ATPases belonging to P-type ATPase family proteins that are membrane-bound pumps involved in the ATP-mediated transport of ions and molecules across the membrane. Flippases flip specific phospholipids from the outer to the inner leaflet of a membrane. All P4-ATPases have one...
4.5K