Lockhead Dean, Schwarz Erich M, O'Hagan Robert, Bellotti Sebastian, Krieg Michael, Barr Maureen M, Dunn Alexander R, Sternberg Paul W, Goodman Miriam B
*Department of Molecular and Cellular Physiology, Stanford University School of Medicine, Stanford, CA 94305.
Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853.
Mol Biol Cell. 2016 Sep 21;27(23):3717-28. doi: 10.1091/mbc.E16-06-0473.
Microtubules contribute to many cellular processes, including transport, signaling, and chromosome separation during cell division (Kapitein and Hoogenraad, 2015). They are comprised of αβ-tubulin heterodimers arranged into linear protofilaments and assembled into tubes. Eukaryotes express multiple tubulin isoforms (Gogonea et al., 1999), and there has been a longstanding debate as to whether the isoforms are redundant or perform specialized roles as part of a tubulin code (Fulton and Simpson, 1976). Here, we use the well-characterized touch receptor neurons (TRNs) of Caenorhabditis elegans to investigate this question, through genetic dissection of process outgrowth both in vivo and in vitro With single-cell RNA-seq, we compare transcription profiles for TRNs with those of two other sensory neurons, and present evidence that each sensory neuron expresses a distinct palette of tubulin genes. In the TRNs, we analyze process outgrowth and show that four tubulins (tba-1, tba-2, tbb-1, and tbb-2) function partially or fully redundantly, while two others (mec-7 and mec-12) perform specialized, context-dependent roles. Our findings support a model in which sensory neurons express overlapping subsets of tubulin genes whose functional redundancy varies between cell types and in vivo and in vitro contexts.
微管参与许多细胞过程,包括细胞分裂过程中的运输、信号传导和染色体分离(Kapitein和Hoogenraad,2015年)。它们由排列成线性原纤维并组装成管的αβ-微管蛋白异二聚体组成。真核生物表达多种微管蛋白异构体(Gogonea等人,1999年),关于这些异构体是冗余的还是作为微管蛋白编码的一部分发挥特殊作用,长期以来一直存在争论(Fulton和Simpson,1976年)。在这里,我们利用模式生物秀丽隐杆线虫中特征明确的触觉感受神经元(TRNs),通过体内和体外对轴突生长的基因剖析来研究这个问题。通过单细胞RNA测序,我们将TRNs的转录谱与另外两种感觉神经元的转录谱进行比较,并提供证据表明每个感觉神经元都表达一组独特的微管蛋白基因。在TRNs中,我们分析了轴突生长情况,发现四种微管蛋白(tba-1、tba-2、tbb-1和tbb-2)部分或完全冗余发挥作用,而另外两种(mec-7和mec-12)则发挥特殊的、依赖于环境的作用。我们的研究结果支持这样一种模型,即感觉神经元表达微管蛋白基因的重叠子集,其功能冗余在不同细胞类型以及体内和体外环境中有所不同。