Epistatic, synthetic, and balancing interactions among tubulin missense mutations affecting neurite growth in Caenorhabditis elegans

• Published in: Molecular biology of the cell Vol. 32; no. 4; pp. 331 - 347
• Main Authors: Lee, Ho Ming Terence, Sayegh, Natalie Yvonne, Gayek, A Sophia, Jao, Susan Laura Javier, Chalfie, Martin, Zheng, Chaogu
• Format: Journal Article
• Language: English
• Published: United States The American Society for Cell Biology 15.02.2021
• ISSN: 1059-1524; 1939-4586
• DOI: 10.1091/mbc.E20-07-0492

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 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 ( ), antimorphic ( ), and neomorphic ( ) 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 and weak alleles of /β-tubulin that had subtle effects and strong alleles of /α-tubulin. We also discovered complex genetic interactions among the tubulin mutations, including the suppression of mutations by intragenic and alleles, additive and synthetic effects between alleles, and unexpected epistasis, in which weaker alleles masked the effects of stronger alleles in inducing ectopic neurite growth. We also observed balancing between and alleles, whose respective MT-hyperstablizing and -destabilizing effects neutralized each other.