LaFerriere Holly, Zars Troy
Division of Biological Sciences, University of Missouri, Columbia, MO 65211, USA.
Division of Biological Sciences, University of Missouri, Columbia, MO 65211, USA.
Neurobiol Learn Mem. 2017 Oct;144:68-76. doi: 10.1016/j.nlm.2017.06.006. Epub 2017 Jun 29.
The tribbles (trbl) pseudokinases play important roles in signaling and physiology in multiple contexts, ranging from innate immunity to cancer, suggesting fundamental cellular functions for the trbls' gene products. Despite expression of the trbl pseudokinases in the nervous systems of invertebrate and vertebrate animals, and evidence that they have a function within mouse and human dopamine neurons, there is no clear case for a function of a Trbl protein that influences behavior. Indeed, the first and only evidence for this type of function comes from Drosophila melanogaster, where a mutation of the single trbl gene was identified in a genetic screen for short-term memory mutant flies. The current study tested flies containing multiple trbl mutant alleles and potential transgenic rescue in both operant place memory and classical olfactory memory paradigms. Genetic complementation tests and transgenic rescue of memory phenotypes in both paradigms show that the D. melanogaster trbl pseudokinase is essential for proper memory formation. Expression analysis with a polyclonal antiserum against Trbl shows that the protein is expressed widely in the fly brain, with higher expression in the cellular rind than the neuropil. Rescue of the behavioral phenotype with transgenic expression indicates the trbl function can be localized to a subset of the nervous system. Thus, we provide the first compelling case for the function of a trbl pseudokinase in the regulation of behavior.
TRIBBLE（TRBL）伪激酶在多种情况下的信号传导和生理学中发挥重要作用，范围从先天免疫到癌症，这表明TRBL基因产物具有基本的细胞功能。尽管TRBL伪激酶在无脊椎动物和脊椎动物的神经系统中表达，并且有证据表明它们在小鼠和人类多巴胺神经元中具有功能，但尚无明确证据表明Trbl蛋白具有影响行为的功能。事实上，这种功能的首个也是唯一证据来自黑腹果蝇，在一项针对短期记忆突变果蝇的遗传筛选中发现了单个trbl基因的突变。当前的研究在操作性位置记忆和经典嗅觉记忆范式中测试了含有多个trbl突变等位基因的果蝇以及潜在的转基因拯救情况。两种范式中的遗传互补测试和记忆表型的转基因拯救表明，黑腹果蝇的trbl伪激酶对于正确的记忆形成至关重要。用针对Trbl的多克隆抗血清进行的表达分析表明，该蛋白在果蝇大脑中广泛表达，在细胞皮层中的表达高于神经纤维网。转基因表达对行为表型的拯救表明trbl功能可定位于神经系统的一个子集。因此，我们首次有力证明了trbl伪激酶在行为调节中的功能。
