环素D1-Cdk4通过对GABAA受体的酸化来调节神经元活动
Neus Pedraza1, Ma Ventura Monserrat2, Francisco Ferrezuelo2
1Cell Cycle, Department of Basic Medical Sciences, Institut de Recerca Biomèdica de Lleida (IRBLLEIDA), University of Lleida, Lleida, Spain. neus.pedraza@udl.cat.
Cellular and molecular life sciences : CMLS
|September 8, 2023
概括
核环素D1 (Ccnd1) 通过与GABA受体相互作用来调节细胞周期和神经元信号传递. 这项研究揭示了Ccnd1
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:
- 核环素D1 (Ccnd1) 是细胞循环进展的关键调节剂.
- 在神经元前体分化过程中,Ccnd1转移到细胞质.
- 成熟神经元中Ccnd1的细胞质功能在很大程度上是未知的.
研究的目的:
- 为了识别Ccnd1在转移后神经元中的细胞质点.
- 阐明Ccnd1-Cdk4在调节神经元信号通路中的作用.
- 研究Ccnd1对GABA受体功能和神经元发育的影响.
主要方法:
- 同免疫沉用于识别Ccnd1相互作用体.
- 在体外激酶试验测试以确定alpha-4上的Ccnd1-Cdk4酸化位.
- 全细胞补丁记录以测量GABAergic电流.
- 在CCND1淘汰赛小鼠中分析树突脊柱形态.
主要成果:
- 甲型GABA受体 (GABAARs) 的α-4 (α4) 子单元被确定为Ccnd1-Cdk4.4的直接相互作用者和基质.
- 在Thr423和Ser431的Ccnd1-Cdk4酸化α4,上调其表面表达并增强GABAAR反应.
- 抑制Cdk4或使用非酸化α4减少突触和突触外电流在老鼠海马.
- CCND1淘汰赛小鼠表现出改变的树突脊柱模式,这些模式被相仿药α4.4所拯救.
结论:
- Ccnd1-Cdk4直接调节中枢神经系统中含有α4的GABAARs的功能和表面表达.
- 这项研究确立了G1环林Ccnd1在调节神经元信号传递和突触可塑性方面的新角色.
- 这些发现提供了细胞循环调节器和成熟大脑中神经递质受体功能之间的分子联系.
相关概念视频
Positive Regulator Molecules
5.5K
Mitotic cell division results in daughter cells that exactly resemble the parent cell. However, errors in the DNA replication or distribution of genetic material may lead to genetic mutations that may be passed down to every new cell formed from the resulting abnormal cell. Propagation of such mutant cells is restricted through checkpoint mechanisms present at different stages of the cell cycle. These checkpoints involve regulator molecules that either promote or demote cell cycle events.
5.5K
GPCRs Regulate Adenylyl Cylase Activity
5.7K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
5.7K
Inhibition of Cdk Activity
4.8K
The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
4.8K
Calmodulin-dependent Signaling
5.2K
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,...
5.2K
Amplifying Signals via Enzymatic Cascade
8.5K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.5K
cAMP-dependent Protein Kinase Pathways
6.4K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
6.4K


