A cAMP receptor-like G protein-coupled receptor with roles in growth regulation and development

A cAMP receptor-like G protein-coupled receptor with roles in growth regulation and development
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DOI:
10.1016/j.ydbio.2003.09.035
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发表时间:
2004-01-15
影响因子:
2.7
通讯作者:
Hadwiger, JA
Hadwiger, JA
中科院分区:
生物学3区
文献类型:
--
作者:
Raisley, B;Zhang, MH;Hadwiger, JA

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盘基网柄菌利用G蛋白介导的信号转导来实现许多营养和发育功能,这表明除了已知的四种环磷酸腺苷(CAMP)受体(cAR1-4)外,还存在G蛋白偶联受体(GPCRs)。CAMP受体序列用于鉴定食道真菌编码cAMP受体样蛋白CRLA-C的基因。这些推测的GPCRs和cAMP受体之间的有限序列同源性表明CRL受体不太可能是cAMP受体。CRL基因在生长和发育生命周期的不同时期表达。单个CRL基因的中断不会损害对叶酸或cAMP的趋化反应,也不会改变cAMP依赖的聚集。然而,CRLA(-)突变体的细胞密度高于野生型细胞,高拷贝数的CRLA表达载体对细胞活力不利,表明CRLA是细胞生长的负调控因子。此外,CRLA(-)突变体产生大的聚集体,导致前端形成延迟,这表明CRLA受体在前柄细胞区的发育中发挥了作用。在嵌合生物的茎前细胞区缺乏表达GFP的CRLA(-)突变体,这支持了CRLA受体在茎前细胞分化中的细胞自主作用。(C)2003 Elsevier Inc.保留所有权利。
Dictyostelium discoideum uses G protein-mediated signal transduction for many vegetative and developmental functions, suggesting the existence of G protein-coupled receptors (GPCRs) other than the four known cyclic adenosine monophosphate (cAMP) receptors (cAR1-4). Sequences of the cAMP receptors were used to identify Dietyostelium genes encoding cAMP receptor-like proteins, CrlA-C. Limited sequence identity between these putative GPCRs and the cAMP receptors suggests the Crl receptors are unlikely to be receptors for cAMP. The crl genes are expressed at various times during growth and the developmental life cycle. Disruption of individual crl genes did not impair chemotactic responses to folic acid or cAMP or alter cAMP-dependent aggregation. However, crlA(-) mutants grew to a higher cell density than did wild-type cells and high-copy-number crlA expression vectors were detrimental to cell viability, suggesting that CrlA is a negative regulator of cell growth. In addition, crlA(-) mutants produce large aggregates with delayed anterior tip formation indicating a role for the CrlA receptor in the development of the anterior prestalk cell region. The scarcity of GFP-expressing crlA(-) mutants in the anterior prestalk cell region of chimeric organisms supports a cell-autonomous role for the CrlA receptor in prestalk cell differentiation. (C) 2003 Elsevier Inc. All rights reserved.