Complex inheritance of the plasmodial surface anion channel in a Plasmodium falciparum genetic cross
Complex inheritance of the plasmodial surface anion channel in a Plasmodium falciparum genetic cross
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DOI：
10.1111/j.1365-2958.2009.06661.x
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发表时间：
2009-04-01
影响因子：
3.6
通讯作者：
Desai, Sanjay A.
中科院分区：
文献类型：
--
作者：
Alkhalil, Abdulnaser;Pillai, Ajay D.;Desai, Sanjay A.
感染了疟原虫的人红细胞对许多溶质的渗透性增加。疟原虫表面阴离子通道（PSAC）可能介导了这些变化。尽管对PSAC的生物化学和生物物理特性有很好的了解，但PSAC活性的遗传基础仍然未知。实验室分离株和两个突变体在体外选择产生的功能多态性牵连寄生虫编码的通道，虽然寄生虫诱导的内源性通道的修改还没有被正式排除。在这里，我们确定了稳定的差异，呋塞米对PSAC活性诱导的HB 3和3D 7A寄生虫。这种差异是明显的，在两个单一的PSAC膜片钳记录和山梨醇介导的渗透溶解测量，确认Cl-和山梨醇是由一个单通道类型的运输。HB 3和3D 7A之间的遗传杂交的19个后代的检查显示复杂的遗传与一些克隆后代表现出呋塞米亲和力的范围外的亲本值。通过3D 7A克隆自交产生的分离物也表现出改变的呋塞米亲和力，暗示减数分裂或通过灵长类宿主期间一个或多个等位基因的变化。PSAC可以由多个寄生虫基因（例如多基因家族或编码不同通道亚基的多个基因）或在强选择压力下的单个多态性基因编码。
Human erythrocytes infected with the malaria parasite Plasmodium falciparum have increased permeabilities to many solutes. The plasmodial surface anion channel (PSAC) may mediate these changes. Despite good understanding of the biochemical and biophysical properties, the genetic basis of PSAC activity remains unknown. Functional polymorphisms in laboratory isolates and two mutants generated by in vitro selection implicate a parasite-encoded channel, although parasite-induced modifications of endogenous channels have not been formally excluded. Here, we identified stable differences in furosemide efficacy against PSAC activity induced by HB3 and 3D7A parasites. This difference was apparent in both single PSAC patch-clamp recordings and in sorbitol-mediated osmotic lysis measurements, confirming that Cl- and sorbitol are transported by a single-channel type. Examination of 19 progeny from a genetic cross between HB3 and 3D7A revealed complex inheritance with some cloned progeny exhibiting furosemide affinities outside the range of parental values. Isolates generated by selfing of the 3D7A clone also exhibited altered furosemide affinities, implicating changes in one or more alleles during meiosis or passage through a primate host. PSAC may be encoded by multiple parasite genes (e.g. a multi-gene family or multiple genes that encode distinct channel subunits) or a single polymorphic gene under strong selective pressure.