Chip is an essential cofactor for apterous in the regulation of axon guidance in Drosophila.
Chip is an essential cofactor for apterous in the regulation of axon guidance in Drosophila.
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发表时间：
2000-05
期刊：
影响因子：
4.6
通讯作者：
D. J. V. Meyel;David D O'Keefe;Stefan Thor;L. Jurata;Gordon N. Gill;John B. Thomas
中科院分区：
文献类型：
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作者：
D. J. V. Meyel;David D O'Keefe;Stefan Thor;L. Jurata;Gordon N. Gill;John B. Thomas
LIM-homeodomain转录因子在神经元亚群中表达，并且是正确的轴突引导和神经递质身份所需的。LIM同源结构域家族成员Apterous需要LIM结合蛋白芯片来执行果蝇翅膀的模式化生长。为了确定芯片是否是一个通用的辅因子在体内的各种LIM同源结构域的功能，我们研究了它在胚胎神经系统中的作用。功能丧失的芯片突变导致神经递质产生缺陷，模仿无翅和胰岛突变体。表达Aptereus的神经元也需要Chip进行细胞自主性以进行适当的轴突引导，并且需要同源二聚化结构域和LIM相互作用结构域两者来适当地发挥功能。使用芯片/无翅嵌合分子缺乏域通常需要它们的相互作用，我们重建的复杂和拯救的轴突指导缺陷的无翅突变体，芯片突变体和胚胎双重突变的无翅和芯片。我们的研究结果表明，芯片参与了一系列的发展计划控制的LIM-homeodomain蛋白质和一个四聚体的复合物，包括两个Apterous分子桥接的芯片同源二聚体的功能单元，通过它Apterous行为在神经元分化。
LIM-homeodomain transcription factors are expressed in subsets of neurons and are required for correct axon guidance and neurotransmitter identity. The LIM-homeodomain family member Apterous requires the LIM-binding protein Chip to execute patterned outgrowth of the Drosophila wing. To determine whether Chip is a general cofactor for diverse LIM-homeodomain functions in vivo, we studied its role in the embryonic nervous system. Loss-of-function Chip mutations cause defects in neurotransmitter production that mimic apterous and islet mutants. Chip is also required cell-autonomously by Apterous-expressing neurons for proper axon guidance, and requires both a homodimerization domain and a LIM interaction domain to function appropriately. Using a Chip/Apterous chimeric molecule lacking domains normally required for their interaction, we reconstituted the complex and rescued the axon guidance defects of apterous mutants, of Chip mutants and of embryos doubly mutant for both apterous and Chip. Our results indicate that Chip participates in a range of developmental programs controlled by LIM-homeodomain proteins and that a tetrameric complex comprising two Apterous molecules bridged by a Chip homodimer is the functional unit through which Apterous acts during neuronal differentiation.