Gα subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae
Gα subunit Gpa2 recruits kelch repeat subunits that inhibit receptor-G protein coupling during cAMP-induced dimorphic transitions in Saccharomyces cerevisiae
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DOI：
10.1091/mbc.e05-05-0403
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发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Heitman, J
中科院分区：
文献类型：
--
作者：
Harashima, T;Heitman, J
所有的真核细胞都通过G蛋白偶联受体（GPCR）和相关的异源三聚体G蛋白来感知细胞外刺激并激活细胞内信号级联。酿酒酵母GPCR Gpr 1和相关的G α亚基Gpa 2感知胞外碳源（包括葡萄糖）以控制丝状生长。与传统的G α亚基相反，Gpa 2与kelch重复G β模拟蛋白Gpb 1和Gpb 2形成非典型G蛋白复合物。Gpb 1/2通过抑制Gpa 2和一个尚未鉴定的靶点来负调节cAMP信号传导。在这里，我们表明，Gpa 2需要其N-末端的膜定位的脂质修饰，但与Gpr 1受体或Gpb 1/2亚基的协会是不确定的膜靶向。相反，Gpa 2促进其相关的G β模拟亚基Gpb 2的膜定位。我们还表明，Gpa 2的N-末端结合到Gpb 2和Gpr 1受体的C-末端尾部，Gpb 1/2结合干扰Gpr 1受体偶联到Gpa 2。我们的研究调用新的机制，涉及GPCR-G蛋白模块，可能是保守的多细胞真核生物。
All eukaryotic cells sense extracellular stimuli and activate intracellular signaling cascades via G protein-coupled receptors (GPCR) and associated heterotrimeric G proteins. The Saccharomyces cerevisiae GPCR Gpr1 and associated G alpha subunit Gpa2 sense extracellular carbon sources (including glucose) to govern filamentous growth. In contrast to conventional G alpha subunits, Gpa2 forms an atypical G protein complex with the kelch repeat G beta mimic proteins Gpb1 and Gpb2. Gpb1/2 negatively regulate cAMP signaling by inhibiting Gpa2 and an as yet unidentified target. Here we show that Gpa2 requires lipid modifications of its N-terminus for membrane localization but association with the Gpr1 receptor or Gpb1/2 subunits is dispensable for membrane targeting. Instead, Gpa2 promotes membrane localization of its associated G beta mimic subunit Gpb2. We also show that the Gpa2 N-terminus binds both to Gpb2 and to the C-terminal tail of the Gpr1 receptor and that Gpb1/2 binding interferes with Gpr1 receptor coupling to Gpa2. Our studies invoke novel mechanisms involving GPCR-G protein modules that may be conserved in multicellular eukaryotes.