细胞染色体c通过干扰Candida albicans中cAMP-PKA信号传递来调节细胞形态发生
Guisheng Zeng1, Xiaoli Xu1, Yee Jiun Kok2
1A(∗)STAR Infectious Diseases Labs (A(∗)STAR ID Labs), Agency for Science, Technology and Research (A(∗)STAR), 8A Biomedical Grove, #05-13 Immunos, Singapore 138648, Singapore.
Cell reports
|November 19, 2023
概括
在Candida albicans中,阻断细胞染色体c的氨酸甲基化,可以阻止细胞的生长. 然而,这种非甲基化形式加速了增殖,在真菌病原体中保持了毒性.
科学领域:
- 微生物学 微生物学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 侵袭性海法生长是人类真菌病原体Candida albicans的关键毒性因素.
- 了解细胞发育的调节对于对抗真菌感染至关重要.
研究的目的:
- 调查CTM1和氨酸甲基化在Candida albicans中细胞生长和毒性的作用.
- 阐明细胞染色体c甲基化影响细胞发育和致病性的分子机制.
主要方法:
- 转子子介导的全基因组突变发生,以确定影响细胞生长的基因.
- 转录组分析以评估突变菌株的基因表达变化.
- 同免疫沉和体外激酶试验用于研究蛋白质相互作用和酶活性.
主要成果:
- lysine甲基转移酶CTM1的失活,通过阻止K79.9的细胞染色体c (Cyc1) 的三甲基化,阻断了细胞的生长.
- 非甲基化Cyc1通过抑制循环AMP-蛋白激酶A (cAMP-PKA) 信号传递来抑制细胞生长,从而导致NRG1抑制剂水平增加.
- 尽管缺陷形形成,ctm1Δ/Δ和cyc1K79A突变表现出加速增殖和保持毒性在小鼠模型.
结论:
- 细胞染色体c lysine甲基化是一种新的调节机制,可以控制Candida albicans的生长和毒性.
- 非甲基化Cyc1在抑制细胞发育方面发挥着关键作用,但促进了增殖,突出显示了与毒性的复杂相互作用.
- 这项研究揭示了氨酸甲基化对细胞染色体c的新生物学功能及其对真菌病原性的影响.
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