TY - JOUR T1 - Distinct effects of tubulin isotype mutations on neurite growth in <em>Caenorhabditis elegans</em> JF - bioRxiv DO - 10.1101/131326 SP - 131326 AU - Chaogu Zheng AU - Margarete Diaz-Cuadros AU - Susan Laura Jao AU - Ken C.Q. Nguyen AU - David H. Hall AU - Martin Chalfie Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/04/26/131326.abstract N2 - Eukaryotic genomes contain multiple tubulin isotypes, and their dominant missense mutations cause a range of neurodevelopmental defects. Using the C. elegans touch receptor neurons, we analyzed the effects of 67 missense mutations in tubulin genes on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations causing mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces and significantly reduced MT stability, causing severe neurite growth defects; 3) neomorphic mutations, which map to the exterior surface and increased MT stability, causing ectopic neurite growth. Importantly, we engineered several disease-associated human tubulin mutations into C. elegans genes and examine their impact on neuronal development. We also discovered a MT-destabilizing α-tubulin isotype, whose loss led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination may be responsible for this destabilization. ER -