Center for Sensory Biology, Johns Hopkins School of Medicine, 430 Rangos Building, 855 N Wolfe St, Baltimore, MD 21205, USA.
Mol Cell Neurosci. 2010 Apr;43(4):353-62. doi: 10.1016/j.mcn.2010.01.002. Epub 2010 Jan 18.
Odorant-evoked activity contributes to olfactory epithelium organization and axon targeting. We examined the consequences on gene expression of a genetic disruption of the channel responsible for olfactory transduction. Genes encoding calcium-binding EF-hand motifs, were among the most highly regulated transcripts consistent with the central role of Ca(2+) influx in neuronal depolarization. Several genes encoding integral membrane proteins are also highly regulated. One gene, Lrrc3b, was regulated more than 10-fold by odorant activity. Changes in expression occur within thirty minutes and are maintained for several hours. In genetic disruptions of Lrrc3b, a Lrrc3b-promoter-driven reporter adopts the activity-regulated expression of the endogenous gene. Individual olfactory glomeruli have a wide spectrum of activity levels that can be modulated by altering odor exposure. The Lrrc3b reporter mouse permits direct assessment of activity in identified glomeruli. In stable odorant environments, activity-regulated proteins provide a characteristic signature that is correlated with the olfactory receptor they express.
气味刺激引发的活动有助于嗅上皮组织的形成和轴突的靶向。我们研究了负责嗅觉转导的通道发生遗传破坏对基因表达的影响。编码钙结合 EF 手模体的基因是受调控最多的转录本之一,这与 Ca2+内流在神经元去极化中的核心作用一致。几种编码完整膜蛋白的基因也受到高度调控。一个基因 Lrrc3b,受气味活性的调节超过 10 倍。表达的变化发生在三十分钟内,并持续数小时。在 Lrrc3b 的遗传破坏中,一个由 Lrrc3b 启动子驱动的报告基因采用了内源性基因的活性调节表达。单个嗅小球具有广泛的活性水平,可以通过改变气味暴露来调节。Lrrc3b 报告基因小鼠允许在已识别的嗅小球中直接评估活性。在稳定的气味环境中,活性调节蛋白提供了与它们表达的嗅觉受体相关的特征性特征。