Cationic pathway of pH regulation in larvae of Anopheles gambiae
Cationic pathway of pH regulation in larvae of Anopheles gambiae
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DOI：
10.1242/jeb.012021
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发表时间：
2008-03-15
影响因子：
2.8
通讯作者：
Harvey, William R.
中科院分区：
文献类型：
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作者：
Okech, Bernard A.;Boudko, Dmitri Y.;Harvey, William R.
冈比亚按蚊幼虫（双翅目：库蚊科）生活在低Na+浓度的淡水中，但它们利用Na+进行消化道碱化、电泳氨基酸摄取和神经功能。幼虫完成这些功能的代谢途径有阴离子和阳离子成分相互作用，使幼虫在排泄H+和HCO3-的同时保存Na+。阴离子途径包括代谢CO2扩散过程、碳酸酐酶和Cl-/HCO3-交换物；它为管腔提供弱HCO3-和弱CO32-阴离子。阳离子途径由H+ v - atp酶和Na+/H+反转运蛋白（NHAs）、Na+/K+ p - atp酶和Na+/H+交换蛋白（NHEs）以及几种（Na+或K+）：氨基酸（+/-）同向转运蛋白，又称营养氨基酸转运蛋白（NATs）组成。本文考虑了阳离子途径，它提供了强Na+或K+阳离子，使前中肠管腔碱化，然后将它们去除，并在后中肠恢复较低的pH值。阳离子途径的一个关键成员是Na+/H+反转运蛋白，最近从冈比亚按蚊幼虫中克隆出来，定位于消化道质膜，并根据其系统发育命名为AgNHA1。对所有克隆的NHA和NHEs的系统发育比较表明，AgNHA1是第一个被克隆和定位的后生动物NHA，它与电泳的原核NHA处于同一进化支，由电致H+ f - atp酶驱动。像原核生物的NHAs一样，AgNHA1被认为是电泳的，由电致H+ v - atp酶驱动。AgNHA1和嗜碱细菌NHAs都面临高碱性环境；为了使蚊子幼虫的中肠腔碱化，AgNHA1就像细菌的NHAs一样，必须向内移动nH(+)，向外移动Na+。可能导致电泳原核NHAs进化的碱性环境也导致了蚊子幼虫中电泳AgNHA1的进化。为了支持这一假设，AgNHA1和H+ v - atp酶的抗体在An中标记相同的膜。冈比亚按蚊的幼虫。H+ v - atp酶与（Na+或K+）：氨基酸（+/-）同调体AgNAT8定位于后中肠细胞的同一顶膜上，构成了降低后中肠管腔pH值的功能等效的NHE。到目前为止，所有表征的NATs都是Na+或K+同源体，因此该推论可能具有广泛的应用。推断出H+ v - atp酶AgNHA1和AgNAT8在该膜上的共定位形成了H+和Na+在后中肠局部循环的途径。局部H+循环可以防止腔内不受控制的酸化，而局部Na+循环可以调节pH并支持Na+：氨基酸（+/-）同调。同时，一个长距离的Na+循环首先将Na+从血液转移到胃caeca和前中肠管腔，在那里开始碱化，然后将Na+从直肠管腔返回到血液，在那里它防止了H+和HCO3排泄过程中Na+的损失。H+ v - atp酶和Na+/K+- atp酶在An中的定位。冈比亚蚊幼虫与报道的埃及伊蚊幼虫相似。推断出这两种atp酶与NHA和NAT在消化道中的共定位构成了Na+保存中肠碱化和去碱化的阳离子途径，这在以前从未报道过。
Anopheles gambiae larvae ( Diptera: Culicidae) live in freshwater with low Na+ concentrations yet they use Na+ for alkalinization of the alimentary canal, for electrophoretic amino acid uptake and for nerve function. The metabolic pathway by which larvae accomplish these functions has anionic and cationic components that interact and allow the larva to conserve Na+ while excreting H+ and HCO3-. The anionic pathway consists of a metabolic CO2 diffusion process, carbonic anhydrase and Cl-/HCO3- exchangers; it provides weak HCO3- and weaker CO32- anions to the lumen. The cationic pathway consists of H+ V-ATPases and Na+/H+ antiporters ( NHAs), Na+/K+ P-ATPases and Na+/H+ exchangers ( NHEs) along with several ( Na+ or K+): amino acid(+/-) symporters, a.k.a. nutrient amino acid transporters ( NATs). This paper considers the cationic pathway, which provides the strong Na+ or K+ cations that alkalinize the lumen in anterior midgut then removes them and restores a lower pH in posterior midgut. A key member of the cationic pathway is a Na+/H+ antiporter, which was cloned recently from Anopheles gambiae larvae, localized strategically in plasma membranes of the alimentary canal and named AgNHA1 based upon its phylogeny. A phylogenetic comparison of all cloned NHAs and NHEs revealed that AgNHA1 is the first metazoan NHA to be cloned and localized and that it is in the same clade as electrophoretic prokaryotic NHAs that are driven by the electrogenic H+ F-ATPase. Like prokaryotic NHAs, AgNHA1 is thought to be electrophoretic and to be driven by the electrogenic H+ V-ATPase. Both AgNHA1 and alkalophilic bacterial NHAs face highly alkaline environments; to alkalinize the larva mosquito midgut lumen, AgNHA1, like the bacterial NHAs, would have to move nH(+) inwardly and Na+ outwardly. Perhaps the alkaline environment that led to the evolution of electrophoretic prokaryotic NHAs also led to the evolution of an electrophoretic AgNHA1 in mosquito larvae. In support of this hypothesis, antibodies to both AgNHA1 and H+ V-ATPase label the same membranes in An. gambiae larvae. The localization of H+ V-ATPase together with ( Na+ or K+): amino acid(+/-) symporter, AgNAT8, on the same apical membrane in posterior midgut cells constitutes the functional equivalent of an NHE that lowers the pH in the posterior midgut lumen. All NATs characterized to date are Na+ or K+ symporters so the deduction is likely to have wide application. The deduced colocalization of H+ V-ATPase, AgNHA1 and AgNAT8, on this membrane forms a pathway for local cycling of H+ and Na+ in posterior midgut. The local H+ cycle would prevent unchecked acidification of the lumen while the local Na+ cycle would regulate pH and support Na+:amino acid(+/-) symport. Meanwhile, a long-range Na+ cycle first transfers Na+ from the blood to gastric caeca and anterior midgut lumen where it initiates alkalinization and then returns Na+ from the rectal lumen to the blood, where it prevents loss of Na+ during H+ and HCO3 excretion.The localization of H+V-ATPase and Na+/K+-ATPase in An. gambiae larvae parallels that reported for Aedes aegypti larvae. The deduced colocalization of the two ATPases along with NHA and NAT in the alimentary canal constitutes a cationic pathway for Na+-conserving midgut alkalinization and de-alkalinization which has never been reported before.