PDF(Pubmed)
Abstract：
Dual-specificity LAMMER kinases are highly evolutionarily conserved in eukaryotes and play pivotal roles in diverse physiological processes, such as growth, differentiation, and stress responses. Although the functions of LAMMER kinase in fungal pathogens in pathogenicity and stress responses have been characterized, its role in Cryptococcus neoformans, a human fungal pathogen and a model yeast of basidiomycetes, remains elusive. In this study, we identified a LKH1 homologous gene and constructed a strain with a deleted LKH1 and a complemented strain. Similar to other fungi, the lkh1Δ mutant showed intrinsic growth defects. We observed that C. neoformans Lkh1 was involved in diverse stress responses, including oxidative stress and cell wall stress. Particularly, Lkh1 regulates DNA damage responses in Rad53-dependent and -independent manners. Furthermore, the absence of LKH1 reduced basidiospore formation. Our observations indicate that Lkh1 becomes hyperphosphorylated upon treatment with rapamycin, a TOR protein inhibitor. Notably, LKH1 deletion led to defects in melanin synthesis and capsule formation. Furthermore, we found that the deletion of LKH1 led to the avirulence of C. neoformans in a systemic cryptococcosis murine model. Taken together, Lkh1 is required for the stress response, sexual differentiation, and virulence of C. neoformans.
摘要：
双特异性LAMMER激酶在真核生物中高度进化保守，在多种生理过程中起关键作用。比如增长，分化,和应激反应。尽管LAMMER激酶在真菌病原体的致病性和应激反应中的功能已经被表征,它在新生隐球菌中的作用，一种人类真菌病原体和担子菌模型酵母，仍然难以捉摸。在这项研究中,我们鉴定了一个LKH1同源基因，并构建了一个缺失LKH1的菌株和一个互补菌株。类似于其他真菌，lkh1Δ突变体显示出内在的生长缺陷。我们观察到C.neoformansLkh1参与不同的应激反应，包括氧化应激和细胞壁应激。特别是,Lkh1以Rad53依赖性和非依赖性方式调节DNA损伤反应。此外，LKH1的缺失减少了担子孢子的形成。我们的观察表明，Lkh1在用雷帕霉素治疗后变得过度磷酸化，TOR蛋白抑制剂。值得注意的是,LKH1缺失导致黑色素合成和囊膜形成缺陷。此外，我们发现，在系统性隐球菌病鼠模型中，LKH1的缺失导致新衣原体的无毒力。一起来看,Lkh1是应激反应所必需的，性分化,和C.新生动物的毒力。
