Department of Biology, Queen's University, Kingston, Ontario, Canada.
Dev Biol. 2011 Jun 1;354(1):55-66. doi: 10.1016/j.ydbio.2011.03.019. Epub 2011 Apr 6.
The NCK adaptor proteins are composed entirely of SH3 and SH2 domains and serve as protein interaction bridges for several receptors during signal transduction events. Here we report the molecular and genetic analysis of the Caenorhabditis elegans nck-1 gene. C. elegans nck-1 encodes two isoforms: NCK-1A and a shorter isoform that lacks the first SH3 domain, NCK-1B. C. elegans nck-1 mutants exhibit defects in axon guidance and neuronal cell position, as well as defects in the excretory canal cell, gonad, and male mating. NCK-1 is broadly expressed in neurons and epithelial cells with NCK-1B being the most abundant isoform. NCK-1A and NCK-1B share a similar expression pattern in parts of the nervous system, but also have independent expression patterns in other tissues. Interestingly, NCK-1B is localized to the nuclei of many cells. Genetic rescue experiments show that NCK-1 functions cell autonomously and, in general, either NCK-1A or NCK-1B is sufficient to function in axon guidance. However, there appears to be specific roles for each isoform, for example NCK-1B is required for HSN cell migration while NCK-1A is required for efficient male mating. Genetic epistasis experiments show that NCK-1 functions redundantly with the LAR Receptor Tyrosine Phosphatase, PTP-3, and the Netrin receptor UNC-40.
NCK 衔接蛋白完全由 SH3 和 SH2 结构域组成，在信号转导过程中充当几种受体的蛋白相互作用桥梁。在这里，我们报告了秀丽隐杆线虫 nck-1 基因的分子和遗传分析。秀丽隐杆线虫 nck-1 编码两种同工型：NCK-1A 和缺乏第一个 SH3 结构域的较短同工型 NCK-1B。秀丽隐杆线虫 nck-1 突变体在轴突导向和神经元细胞位置以及排泄道细胞、性腺和雄性交配中存在缺陷。NCK-1 在神经元和上皮细胞中广泛表达，其中 NCK-1B 是最丰富的同工型。NCK-1A 和 NCK-1B 在神经系统的某些部分具有相似的表达模式，但在其他组织中也具有独立的表达模式。有趣的是，NCK-1B 定位于许多细胞的细胞核中。遗传拯救实验表明，NCK-1 具有细胞自主性，通常，NCK-1A 或 NCK-1B 足以在轴突导向中发挥作用。然而，每种同工型似乎都具有特定的作用，例如，NCK-1B 是 HSN 细胞迁移所必需的，而 NCK-1A 是有效雄性交配所必需的。遗传上位性实验表明，NCK-1 与 LAR 受体酪氨酸磷酸酶、PTP-3 和 Netrin 受体 UNC-40 具有冗余功能。
