Steroids initiate a signaling cascade that triggers rapid sporulation in Dictyostelium
Steroids initiate a signaling cascade that triggers rapid sporulation in Dictyostelium
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DOI：
10.1242/dev.032607
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发表时间：
2009-03-01
期刊：
影响因子：
4.6
通讯作者：
Loomis, William F.
中科院分区：
文献类型：
--
作者：
Anjard, Christophe;Su, Yongxuan;Loomis, William F.
盘基网柄藻前孢子细胞的包囊化受细胞间信号的控制，以确保子实体形成的适当时机。酰基辅酶A结合蛋白AcbA由前孢子细胞分泌，并由前茎蛋白酶TagC加工形成34个氨基酸的肽SDF-2，其触发快速包封。当γ-氨基丁酸（GABA）从前孢子细胞释放并与G蛋白偶联受体（GPCR）GrlE结合时，AcbA被分泌。在缺乏G α亚基和GPCR的突变株中，无论是作为纯群体还是当与其他突变株混合时，对SDF-2产生的分析揭示了GrlA、G α 4和G α 7的非细胞自主作用。我们发现，Ga 7是必不可少的GABA的反应，并可能耦合到GrlE。GrlA-null和G α 4-null细胞对GABA的反应正常，但不能分泌GABA，我们发现它们是对一种疏水性小分子SDF-3的反应所必需的，SDF-3在高潮后期释放。发育过程中类固醇生成的药理学抑制阻断了SDF-3的产生。此外，对SDF-3的反应可以被类固醇拮抗剂米非司酮阻断，而氢化可的松和其他类固醇在纳摩尔范围内加入时模仿SDF-3的作用。似乎SDF-3是一种类固醇，其通过GPCR GrlA与含有G α 4亚基的G蛋白偶联作用来促进GABA的快速释放。SDF-3位于级联的前端，放大封装信号以确保孢子的快速同步形成。
Encapsulation of prespore cells of Dictyostelium discoideum is controlled by several intercellular signals to ensure appropriate timing during fruiting body formation. Acyl-CoA-binding protein, AcbA, is secreted by prespore cells and processed by the prestalk protease TagC to form the 34 amino acid peptide SDF-2 that triggers rapid encapsulation. AcbA is secreted when gamma-aminobutyric acid (GABA) is released from prespore cells and binds to GrlE, a G protein-coupled receptor (GPCR). Analysis of SDF-2 production in mutant strains lacking G alpha subunits and GPCRs, either as pure populations or when mixed with other mutant strains, uncovered the non-cell-autonomous roles of GrlA, G alpha 4 and G alpha 7. We found that Ga7 is essential for the response to GABA and is likely to be coupled to GrlE. GrlA-null and G alpha 4-null cells respond normally to GABA but fail to secrete it. We found that they are necessary for the response to a small hydrophobic molecule, SDF-3, which is released late in culmination. Pharmacological inhibition of steroidogenesis during development blocked the production of SDF-3. Moreover, the response to SDF-3 could be blocked by the steroid antagonist mifepristone, whereas hydrocortisone and other steroids mimicked the effects of SDF-3 when added in the nanomolar range. It appears that SDF-3 is a steroid that elicits rapid release of GABA by acting through the GPCR GrlA, coupled to G protein containing the G alpha 4 subunit. SDF-3 is at the head of the cascade that amplifies the signal for encapsulation to ensure the rapid, synchronous formation of spores.