Peptide signaling during terminal differentiation of Dictyostelium
Peptide signaling during terminal differentiation of Dictyostelium
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DOI：
10.1073/pnas.0501820102
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发表时间：
2005-05-24
影响因子：
11.1
通讯作者：
Loomis, WF
中科院分区：
文献类型：
--
作者：
Anjard, C;Loomis, WF
在后生动物中，细胞间通讯的机制已经进化出了很多种，但其中一些信号分子已经在它们的前辈中使用。社会性变形虫盘基网柄阿米巴（Dictyosteelium discoideum）已知使用肽来触发子实体内的孢子形成，但其序列尚未确定。我们发现，肽信号孢子分化因子2（SDF-2）是从酰基辅酶A结合蛋白，AcbA加工。AcbA的哺乳动物同系物被加工成地西泮结合抑制剂，其结合脑中的GABA（A）受体和外周1，4苯二氮卓受体。虽然网骨藻既没有GABAA也没有外周型苯二氮卓受体，但我们发现地西泮结合抑制剂肽和地西泮（安定）都可以在网骨藻生物测定中模拟SDF-2。缺乏AcbA的突变体只有在与WT细胞的嵌合体中发育时才能很好地形成孢子。使用酵母系统，我们表明与SDF-2受体组胺酸激酶DhkA结合的配体会抑制磷酸化，这可以解释其诱导快速孢子形成的能力。
A wide variety of mechanisms have evolved for intercellular communication in metazoans, but some of the signaling molecules were already used in their predecessors. The social amoeba, Dictyostelium discoideum, is known to use peptides to trigger sporulation within fruiting bodies, but their sequences have not been defined. We found that the peptide signal spore differentiation factor 2 (SDF-2) is processed from acyl-CoA binding protein, AcbA. The mammalian homolog of AcbA is processed to diazepam binding inhibitor that binds to the GABA(A) receptor in the brain and to peripheral 1,4 benzodiazepine receptors. Although Dictyostelium has neither GABAA nor peripheral-type benzodiazepine receptors, we find that both a diazepam binding inhibitor peptide and diazepam (Valium) can mimic SDF-2 in a Dictyostelium bioassay. Mutants lacking AcbA sporulate well only when developed in chimeras with WT cells. Using a yeast system we show that ligand binding to the SDF-2 receptor histidine kinase, DhkA, inhibits phosphorelay, which can account for its ability to induce rapid sporulation.