Kim J Y, Borleis J A, Devreotes P N
Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Dev Biol. 1998 May 1;197(1):117-28. doi: 10.1006/dbio.1998.8882.
One of the common functional features among G-protein coupled receptors is the occurrence of multiple subtypes involved in similar signal transduction events. The cAMP chemoattractant receptor family of Dictyostelium discoideum is composed of four receptors (cAR1-cAR4), which are expressed sequentially throughout the developmental transition from a unicellular to a multicellular organism. The receptors differ in affinity for cAMP and in the sequences of their C-terminal domains. In this study, we constitutively expressed cAR1, cAR2, and cAR3 as well as a series of chimeric and mutant receptors and assessed the capacity of each to mediate chemotaxis, activation of adenylyl cyclase and actin polymerization, and rescue the developmental defect of car1-/car3- cells. We found that various receptors and mutants sense different concentration ranges of cAMP but all can mediate identical responses during the aggregation stage of development. The responses displayed very similar kinetics, suggesting no major differences in regulatory properties attributable to the C-terminal domains. We speculate that switching of receptor subtypes during development enables the organism to respond to the changing concentrations of the chemoattractant and thereby program morphogenesis appropriately.
G蛋白偶联受体的常见功能特征之一是,存在多种参与相似信号转导事件的亚型。盘基网柄菌的cAMP趋化受体家族由四种受体(cAR1 - cAR4)组成,这些受体在从单细胞生物向多细胞生物发育转变的过程中依次表达。这些受体对cAMP的亲和力以及其C末端结构域的序列各不相同。在本研究中,我们组成型表达了cAR1、cAR2和cAR3以及一系列嵌合受体和突变受体,并评估了它们各自介导趋化作用、激活腺苷酸环化酶和肌动蛋白聚合的能力,以及挽救car1 - /car3 - 细胞发育缺陷的能力。我们发现,各种受体和突变体感知不同浓度范围的cAMP,但在发育的聚集阶段都能介导相同的反应。这些反应表现出非常相似的动力学,表明C末端结构域在调节特性上没有重大差异。我们推测,发育过程中受体亚型的转换使生物体能够对趋化剂浓度的变化做出反应,从而适当地规划形态发生。