活动依赖的IGF-1外细胞分裂是由Ca2+传感器synaptotagmin-10控制的
Peng Cao1, Anton Maximov, Thomas C Südhof
1Department of Molecular and Cellular Physiology, and Howard Hughes Medical Institute, Stanford University, 1050 Arastradero Rd., Palo Alto, California 94305, USA.
Cell
|April 19, 2011
概括
合成10 (Syt10) 作为传感器,触发嗅球神经元的胰岛素样生长因子-1 (IGF-1) 分泌. 这一发现揭示了神经元中依赖的外细胞形成的新途径.
科学领域:
- 神经科学是一个神经科学.
- 细胞生物学 细胞生物学
- 分子生物学分子生物学
背景情况:
- 突触胺 (Syts) 是已知的Ca(2+) 传感器,用于表细胞突变,其中Syt1,Syt2,Syt7和Syt9具有特征.
- 其他Syt家族成员的功能,包括Syt10在外细胞形成中的功能,在很大程度上是未知的.
研究的目的:
- 为了研究Syt10在嗅球神经元中的功能.
- 确定负责活动依赖IGF-1分泌的Ca2+) 传感器.
主要方法:
- 研究了Syt10在嗅觉球泡神经元中的作用,使用遗传删除 (淘汰赛) 和外源IGF-1救援.
- 检查了Syt10与IGF-1在体膜囊中的局部化.
- 研究了由Syt10触发的IGF-1的Ca(2+) 依赖的表细胞分裂.
主要成果:
- 嗅球神经元通过一种活动依赖的外细胞分裂途径分泌IGF-1.
- 在这些神经元中,Syt10充当IGF-1外细胞形成的Ca2+传感器.
- 删除Syt10导致神经元变小,突触数量减少,以及IGF-1分泌受损,而外源IGF-1可以逆转这种情况.
- Syt10在囊泡中与IGF-1结合,并通过Ca2+触发的IGF-1分泌物进行介导.
结论:
- 在嗅球神经元中,Syt10调节了一种新的,以前未被识别的,依赖于Ca2+的IGF-1外细胞形成途径.
- 这种Syt10介导的途径与Syt1控制的突触囊泡外细胞形成不同.
- 神经元可以利用不同的突触胺来调节功能上单独的Ca2+依赖的膜融合事件.
相关概念视频
Overview of Secretory Vesicles
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...
Insulin Secretory Vesicles
Insulin secretory vesicles release insulin to stimulate blood glucose uptake and regulate carbohydrate metabolism. When the blood glucose levels increase, glucose enters the pancreatic β-islet cells through glucose transporters. Once inside, glucose is metabolized through glycolysis, the citric acid cycle, and the electron transport chain, producing ATP. This increase in ATP concentration closes ATP-sensitive potassium channels, leading to depolarization of the membrane and the opening of...
Activation and Inactivation of G Proteins
Heterotrimeric G proteins are guanine nucleotide-binding proteins. As the name suggests, heterotrimeric G proteins are composed of three subunits: alpha, beta, and gamma. They remain GDP-bound or GTP-bound inside the cells and switch between inactive/active states. The Gα subunit possesses the nucleotide-binding pocket that binds guanine nucleotides and switches between GDP or GTP-bound states. In contrast, the Gꞵ and Gγ subunits are always bound together with high affinity and are together...
IP3/DAG Signaling Pathway
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 produces two-second...
Feedback Regulation of Calcium Concentration
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...
Calmodulin-dependent Signaling
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,...


