A role for adenosine deaminase in Drosophila larval development.
A role for adenosine deaminase in Drosophila larval development.
复制标题
腺苷脱氨酶在果蝇幼虫发育中的作用。
DOI：
10.1371/journal.pbio.0030201
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发表时间：
2005-07
期刊：
影响因子：
9.8
通讯作者：
Bryant, Peter J
中科院分区：
文献类型：
--
作者：
Dolezal, Tomas;Dolezelova, Eva;Zurovec, Michal;Bryant, Peter J
腺苷脱氨酶（ADA）是一种存在于所有生物体中的酶，催化腺苷和脱氧腺苷不可逆脱氨基为肌苷和脱氧肌苷。腺苷和脱氧腺苷都是具有生物活性的嘌呤，可以对细胞生理学产生深远的影响；值得注意的是，人类缺乏 ADA 会导致严重的联合免疫缺陷。我们建立了果蝇模型，通过基因消除腺苷脱氨酶相关生长因子-A (ADGF-A) 来研究体内腺苷水平改变的影响，ADGF-A 具有 ADA 活性，在肠道和造血器官中表达。在这里，我们证明血细胞（血细胞）是果蝇幼虫中腺苷的主要调节因子，正如之前对哺乳动物的推测一样。由于缺乏 ADGF-A，血淋巴中腺苷水平升高，导致明显不一致的表型效应：一方面包括巨噬细胞样细胞分化和脂肪体分解的早熟变态变化，另一方面发育延迟和蛹化受阻。蛹化的阻断似乎涉及通过腺苷受体 (AdoR) 的信号传导，但血细胞作用促进的脂肪体分解似乎与 AdoR 无关。这种独立机制的存在也被认为存在于哺乳动物中。腺苷脱氨酶对于生存至关重要；人类先天性缺陷会导致严重的免疫缺陷。在这里，作者证明果蝇的腺苷脱氨酶缺乏会导致严重的发育缺陷。
Adenosine deaminase (ADA) is an enzyme present in all organisms that catalyzes the irreversible deamination of adenosine and deoxyadenosine to inosine and deoxyinosine. Both adenosine and deoxyadenosine are biologically active purines that can have a deep impact on cellular physiology; notably, ADA deficiency in humans causes severe combined immunodeficiency. We have established a Drosophila model to study the effects of altered adenosine levels in vivo by genetic elimination of adenosine deaminase-related growth factor-A (ADGF-A), which has ADA activity and is expressed in the gut and hematopoietic organ. Here we show that the hemocytes (blood cells) are the main regulator of adenosine in the Drosophila larva, as was speculated previously for mammals. The elevated level of adenosine in the hemolymph due to lack of ADGF-A leads to apparently inconsistent phenotypic effects: precocious metamorphic changes including differentiation of macrophage-like cells and fat body disintegration on one hand, and delay of development with block of pupariation on the other. The block of pupariation appears to involve signaling through the adenosine receptor (AdoR), but fat body disintegration, which is promoted by action of the hemocytes, seems to be independent of the AdoR. The existence of such an independent mechanism has also been suggested in mammals. Adenosine deaminase is critically important to survival; congenital deficiency in humans leads to severe immunodeficiency. Here, the authors demonstrate that adenosine deaminase deficiency in flies results in severe developmental defects.