AMPylation调节了5'-3'外核酶的PLD3处理过程.
Laura Hoffmann1, Eva-Maria Eckl2, Marleen Bérouti2
1Department of Chemistry, LMU Munich, 81377, Munich, Germany.
Molecular & cellular proteomics : MCP
|August 15, 2025
概括
由FICD监管的脂酶D3 (PLD3) AMPylation对其活动和处理至关重要. 在帕金森病中改变了PLD3调节.
科学领域:
- 分子生物学分子生物学
- 神经科学是一个神经科学.
- 免疫学 免疫学 免疫学
背景情况:
- 脂酶D3 (PLD3) 是一种参与免疫反应和神经元健康的5'-3'外核酶.
- PLD3经历了翻译后修改 (PTMs),包括N-糖化,AMPylation和蛋白质分解裂变.
- 它在阿尔茨海默病 (AD) 中的作用是已知的,但免疫和神经元细胞中的调节机制和功能尚不清楚.
研究的目的:
- 调查PLD3AMPylation的功能影响及其与FICD的相互作用.
- 为了检查帕金森病 (PD) 患者衍生的神经元中PLD3处理的变化.
- 阐明AMPylation在PLD3激活,催化活性和细胞局部化中的作用.
主要方法:
- 识别PLD3 AMPylation网站. 这是一个很好的方法.
- 对AMPylation位点的突变,以评估对PLD3激活和活性的影响.
- 过度表达FICD以研究其对PLD3降解和细胞应激的影响.
- 在PD患者衍生的神经元中对PLD3调节的分析.
主要成果:
- 在可溶性区域中确定了PLD3AMPylation位点,它们的突变损害了PLD3的激活和催化活性.
- FICD过度表达加速了PLD3降解,并诱导了细胞应激.
- 与健康对照人群相比,PD衍生神经元中的PLD3调节发生了改变.
结论:
- AMPylation对PLD3处理和催化活性进行了关键调节.
- 结果提供了对PLD3传输和 lysosomal定位的见解.
- 改变PD中的PLD3调节突出了其在神经退行性疾病中的作用.
相关概念视频
Chromatin Structure Regulates pre-mRNA Processing
7.2K
In eukaryotic cells, nascent mRNA transcripts need to undergo many post-transcriptional modifications to reach the cell cytoplasm and translate into functional proteins. For a long time, transcription and pre-mRNA processing were considered two independent events that occur sequentially in the cell. However, it has now been well established that transcription and pre-mRNA processing are two simultaneous processes that are precisely regulated inside the cell.
The chromatin structure, especially...
The chromatin structure, especially...
7.2K
mRNA Stability and Gene Expression
5.7K
The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
Cis-acting Elements involved in mRNA stability
Cis-acting Elements involved in mRNA stability
5.7K
Pre-mRNA Processing: Modification of pre-mRNA Ends
9.8K
In eukaryotic cells, transcripts made by RNA polymerase are modified and processed before exiting the nucleus. Unprocessed RNA is called precursor mRNA or pre-mRNA to distinguish it from mature mRNA.
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
Once about 20-40 ribonucleotides have been joined together by RNA polymerase, a group of enzymes adds a cap to the 5' end of the growing transcript. In this process, a 5' phosphate is replaced by modified guanosine that has a methyl group attached (7-methyl guanosine). This 5' cap helps...
9.8K
Translesion DNA Polymerases
10.1K
Translesion (TLS) polymerases rescue stalled DNA polymerases at sites of damaged bases by replacing the replicative polymerase and installing a nucleotide across the damaged site. Doing so, TLS allows additional time for the cell to repair the damage before resuming regular DNA replication.
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
TLS polymerases are found in all three domains of life - archaea, bacteria, and eukaryotes. Of the different classes of TLS polymerases, members of the Y family are fitted with specialized structures that...
10.1K
Nonsense-mediated mRNA Decay
10.8K
The Upf proteins that carry out nonsense-mediated decay (NMD) are found in all eukaryotic organisms, including humans. Each protein has an individual role, but they need to work in collaboration. Upf1 is an ATP-dependent RNA helicase that unwinds the RNA helix. Because Upf1 can unwind any RNA, Upf2 and Upf3 are required to help Upf1 discriminate between nonsense and normal mRNAs.
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
Usually, Upf3 binds to an Exon Junction Complex (EJC) at mRNA splice sites. If a ribosome fully translates the mRNA,...
10.8K
Nuclear Export of mRNA
7.9K
Before mRNAs are exported to the cytoplasm, it is crucial to check each mRNA for structural and functional integrity. Eukaryotic cells use several different mechanisms, collectively known as mRNA surveillance, to look for irregularities in mRNAs. Irregular or aberrant mRNA are rapidly degraded by various enzymes. If a defective mRNA escapes the surveillance, it would be translated into a protein which would either be non-functional or not function properly. One of the primary irregularities in...
7.9K


