通过调节cAMP水平,PhoP将应激反应与细胞内生存相结合
Hina Khan1, Partha Paul1, Harsh Goar1
1CSIR, Institute of Microbial Technology, Chandigarh, India.
eLife
|May 13, 2024
概括
结核菌菌的生存依赖于PhoP调节器. PhoP通过抑制Rv0805,一种固酶来控制循环腺单酸盐 (cAMP) 水平,影响细菌的应激耐受性和生存.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 病变的发生和发病.
背景情况:
- 结核菌菌在宿主巨细胞中的生存对于疾病的持续性至关重要.
- 毒性调节剂PhoP对于M.结核病的生存至关重要,但其确切的作用尚不清楚.
- 循环腺单酸盐 (cAMP) 作为影响微生物病原体反应的第二信使.
研究的目的:
- 调查PhoP在调节M.结核病细胞内cAMP水平中的作用.
- 阐明PhoP影响细菌应激耐受性和生存的机制.
主要方法:
- 转录组分析以确定PhoP调节的基因.
- 电泳运动转移试验 (EMSA) 证实PhoP与rv0805促进体结合.
- 对M.结核病进行基因操纵,以非活化PhoP或过度表达Rv0805.5.
- 测量细胞内cAMP水平的测量.
主要成果:
- PhoP作为cAMP特异性化酶Rv0805.5的抑制剂起作用.
- PhoP直接与rv0805基因的促进子区域结合.
- 删除phoP或rv0805的异位表达导致细胞内cAMP水平降低.
- 对PhoP-Rv0805-cAMP通路的失活会降低M.结核病的应激耐受性和细胞内生存率.
结论:
- PhoP通过抑制Rv0805固酶活性来调节M.结核病细胞内cAMP水平.
- 通过PhoP调节cAMP的控制对于细菌应激适应和巨细胞内的生存至关重要.
- 针对这种途径可以为结核病治疗提供新的策略.
相关概念视频
cAMP-dependent Protein Kinase Pathways
6.3K
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,...
6.3K
mTOR Signaling and Cancer Progression
3.8K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.8K
Intracellular Signaling Cascades
46.7K
Once a ligand binds to a receptor, the signal is transmitted through the membrane and into the cytoplasm. The continuation of a signal in this manner is called signal transduction. Signal transduction only occurs with cell-surface receptors, which cannot interact with most components of the cell, such as DNA. Only internal receptors can interact directly with DNA in the nucleus to initiate protein synthesis. When a ligand binds to its receptor, conformational changes occur that affect the...
46.7K
GPCRs Regulate Adenylyl Cylase Activity
5.5K
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...
5.5K
Calmodulin-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
Interactions Between Signaling Pathways
6.3K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.3K


