Cytokinesis of Trypanosoma brucei bloodstream forms depends on expression of adenylyl cyclases of the ESAG4 or ESAG4‐like subfamily
Cytokinesis of Trypanosoma brucei bloodstream forms depends on expression of adenylyl cyclases of the ESAG4 or ESAG4‐like subfamily
复制标题
DOI：
10.1111/j.1365-2958.2012.08013.x
复制
发表时间：
2012-04
影响因子：
3.6
通讯作者：
D. Salmon;S. Bachmaier;Carsten Krumbholz;Markus Kador;J. Gossmann;P. Uzureau;E. Pays;M. Boshart
中科院分区：
文献类型：
--
作者：
D. Salmon;S. Bachmaier;Carsten Krumbholz;Markus Kador;J. Gossmann;P. Uzureau;E. Pays;M. Boshart
布鲁氏锥虫的抗原变异是通过多个端粒表达位点（ESs）的单等位基因表达变异表面糖蛋白（VSG）来实现的。这些ESs中的每一个都含有一个长多顺反子转录单元，其中包含几个表达位点相关基因（esag）。ESAG4拷贝编码血流阶段特异性腺苷酸环化酶（AC），属于一个更大的基因家族，大约有80个成员，其中大多数被称为ESAG4相关基因（GRESAG4s），不编码在ESs中，并且在生命周期中组成性表达。在这里，我们报道了从活性ES中去除ESAG4不会影响寄生虫的生长，无论是在培养中还是在啮齿动物感染中，也不会显著改变总AC活性。相比之下，诱导性RNAi介导的AC亚家族（包括ESAG4和两个ESAG4样GRESAG4 （ESAG4L）基因）的敲低，降低了AC的总活性，并诱导了与细胞分裂受损相关的致死表型。在Δesag4细胞系中观察到明显功能冗余的ESAG4L基因代偿上调，这表明ESAG4/ESAG4L‐亚家族ACs参与细胞分裂的控制。如何解除管制腺苷酸环化酶或cAMP可能损害细胞分裂的讨论。
Antigenic variation of the parasite Trypanosoma brucei operates by monoallelic expression of a variant surface glycoprotein (VSG) from a collection of multiple telomeric expression sites (ESs). Each of these ESs harbours a long polycistronic transcription unit containing several expression site‐associated genes (ESAGs). ESAG4 copies encode bloodstream stage‐specific adenylyl cyclases (AC) and belong to a larger gene family of around 80 members, the majority of which, termed genes related to ESAG4 (GRESAG4s), are not encoded in ESs and are expressed constitutively in the life cycle. Here we report that ablation of ESAG4 from the active ES did not affect parasite growth, neither in culture nor upon rodent infection, and did not significantly change total AC activity. In contrast, inducible RNAi‐mediated knock‐down of an AC subfamily that includes ESAG4 and two ESAG4‐like GRESAG4 (ESAG4L) genes, decreased total AC activity and induced a lethal phenotype linked to impaired cytokinesis. In the Δesag4 line compensatory upregulation of apparently functionally redundant ESAG4L genes was observed, suggesting that the ESAG4/ESAG4L‐subfamily ACs are involved in the control of cell division. How deregulated adenylyl cyclases or cAMP might impair cytokinesis is discussed.