Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms
Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms
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DOI：
10.1038/s41467-020-16593-y
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发表时间：
2020-06-02
影响因子：
16.6
通讯作者：
Pain, Arnab
中科院分区：
文献类型：
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作者：
Subudhi, Amit K.;O'Donnell, Aidan J.;Pain, Arnab
疟原虫在24小时内完成其红细胞内发育周期（IDC），这表明其具有昼夜节律基础，但控制这种周期性的机制尚不清楚。结合体内和体外方法，利用啮齿动物和人类疟疾寄生虫，我们发现：(i) 57%的chabaudi疟原虫基因在转录中表现出每日节律；（ii）当IDC与宿主节律不同步时，58%的这些基因失去转录节律性；（iii） 6%的恶性疟原虫基因在自由运行条件下表现出24小时的表达节律；（iv）蛇形素受体10 （Serpentine receptor 10, SR10）的转录周期为24h，在啮齿动物疟原虫中阻断SR10可使其转录周期缩短2 ~ 3h；(v)多种过程，包括DNA复制、泛素和蛋白酶体途径，受到与宿主节律失去协调和SR10中断的影响。我们的研究结果表明，疟疾寄生虫至少在一定程度上负责调度IDC并协调其与宿主日常节律的发展。
Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.