Mutations in tubulins affect microtubule (MT) dynamics and functions during neuronal differentiation and their genetic interaction provides insights into the regulation of MT functions. We previously used C. elegans touch receptor neurons to analyze the cellular impact of tubulin mutations and reported the phenotypes of 67 tubulin missense mutations, categorized into three classes: loss-of-function (lf), antimorphic (anti), and neomorphic (neo) alleles. In this study, we isolated 54 additional tubulin alleles through suppressor screens in sensitized backgrounds that caused excessive neurite growth. These alleles included 32 missense mutations not analyzed before, bringing the total number of mutations in our collection to 99. Phenotypic characterization of these newly isolated mutations identified three new types of alleles: partial lf and weak neo alleles of mec-7/β-tubulin that had subtle effects and strong anti alleles of mec-12/α-tubulin. We also discovered complex genetic interactions among the tubulin mutations, including the suppression of neo mutations by intragenic lf and anti alleles, additive and synthetic effects between mec-7 neo alleles, and unexpected epistasis, in which weaker neo alleles masked the effects of stronger neo alleles in inducing ectopic neurite growth. We also observed balancing between neo and anti alleles, whose respective MT-hyperstablizing and -destabilizing effects neutralized each other.

微管蛋白中的突变会影响神经元分化过程中的微管 (MT) 动力学和功能，它们的遗传相互作用提供了对 MT 功能调节的见解。我们之前使用秀丽隐杆线虫触摸受体神经元来分析微管蛋白突变对细胞的影响，并报告了 67 种微管蛋白错义突变的表型，分为三类：功能丧失 ( lf )、反形态 ( anti ) 和新形态( neo) 等位基因。在这项研究中，我们通过在致敏背景中通过抑制筛选分离了 54 个额外的微管蛋白等位基因，这会导致神经突过度生长。这些等位基因包括32个错义突变没有分析之前，将突变的总数我们的集合中确定了这些新分离的突变三种新类型的等位基因的99表型特征：局部LF和弱新的等位基因MEC-7 /β微管蛋白对mec-12 /α-微管蛋白具有微妙的作用和强大的抗等位基因。我们还发现了微管蛋白突变之间的复杂遗传相互作用，包括抑制新的基因内突变LF和抗等位基因、mec-7 neo等位基因之间的累加和合成效应以及意外的上位性，其中较弱的neo等位基因掩盖了较强的neo等位基因在诱导异位轴突生长方面的作用。我们还观察到Neo和anti等位基因之间的平衡，它们各自的 MT 超稳定和不稳定效应相互抵消。