Loss of cAMP-specific phosphodiesterase rescues spore development in G protein mutant in dictyostelium.
Loss of cAMP-specific phosphodiesterase rescues spore development in G protein mutant in dictyostelium.
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DOI：
10.1016/j.cellsig.2013.10.003
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发表时间：
2014-02
影响因子：
4.8
通讯作者：
Hadwiger JA
中科院分区：
文献类型：
--
作者：
Schwebs DJ;Nguyen HN;Miller JA;Hadwiger JA
环磷酸腺苷(CAMP)是许多G蛋白介导的信号通路的重要细胞内信号分子，但cAMP信号在具有多条信号通路的细胞中的特异性尚不清楚。在网柄苔藓中，至少有两条不同的G蛋白信号通路由Gα2和Gα4亚基介导，参与cAMP的积累、孢子的产生和趋化作用，这些通路的刺激导致ERK2的激活，ERK2是一种丝裂原激活的蛋白激酶，可以下调cAMP特异性的磷酸二酯酶RegA。在gα2−和gα4−细胞中破坏RegA基因，以确定这种磷酸二酯酶的缺失是否像ERK2−突变那样挽救了这些G蛋白突变体的发育。RegA−突变对发育形态无明显影响，但使Gα突变细胞在嵌合聚合体中分布于前孢子/前柄边缘。RegA功能丧失对G-α-4介导的叶酸趋化作用无影响。然而，在gα4−细胞中的RegA基因的破坏，而在gα2−细胞中的破坏，导致了孢子生产的大量挽救和加速。这种在孢子形成中的拯救需要细胞自主信号，因为早熟孢子形成不能通过嵌合聚合体中的细胞间信号诱导。然而，来自RegA−菌株的胞间信号增加了前茎基因ecmB的表达，并加速了茎细胞的空泡化。来自gα4−Rega−菌株的细胞间信号不诱导ECMA基因的表达，表明在促进柄前细胞发育方面具有细胞类型特异性。在G-α-4HC(G-α-4过表达)株中，RegA基因的破坏不会导致早熟或柄细胞发育，这表明即使在提供野生型细胞间信号的情况下，G-α-4亚单位的高表达也可以掩盖Rega-−相关表型。这些发现表明，Gα2和Gα4介导的途径对孢子和柄细胞的发育有不同的贡献，缺乏RegA功能可以绕过G蛋白调控的孢子发育中的某些缺陷。
Cyclic AMP (cAMP) is an important intracellular signaling molecule for many G protein-mediated signaling pathways but the specificity of cAMP signaling in cells with multiple signaling pathways is not well-understood. In Dictyostelium, at least two different G protein signaling pathways, mediated by the Gα2 and Gα4 subunits, are involved with cAMP accumulation, spore production, and chemotaxis and the stimulation of these pathways results in the activation of ERK2, a mitogen-activated protein kinase that can down regulate the cAMP-specific phosphodiesterase RegA. The regA gene was disrupted in gα2− and gα4− cells to determine if the absence of this phosphodiesterase rescues the development of these G protein mutants as it does for erk2− mutants. The regA− mutation had no major effects on developmental morphology but enriched the distribution of the Gα mutant cells to the prespore/prestalk border in chimeric aggregates. The loss of RegA function had no effect on Gα4-mediated folate chemotaxis. However, the regA gene disruption in gα4− cells, but not in gα2− cells, resulted in a substantial rescue and acceleration of spore production. This rescue in sporulation required cell autonomous signaling because the precocious sporulation could not be induced through intercellular signaling in chimeric aggregates. However, intercellular signals from regA− strains increased the expression of the prestalk gene ecmB and accelerated the vacuolization of stalk cells. Intercellular signaling from gα4−regA− strain did not induce ecmA gene expression indicating cell-type specificity in the promotion of prestalk cell development. regA gene disruption in a Gα4HC (Gα4 overexpression) strain did not result in precocious sporulation or stalk cell development indicating that elevated Gα4 subunit expression can mask regA− associated phenotypes even when provided with wild-type intercellular signaling. These finding indicate that the Gα2 and Gα4-mediated pathways provide different contributions to the development of spores and stalk cells and that the absence of RegA function can bypass some but not all defects in G protein regulated spore development.
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