@article {Zheng131326, author = {Chaogu Zheng and Margarete Diaz-Cuadros and Susan Laura Jao and Ken C.Q. Nguyen and David H. Hall and Martin Chalfie}, title = {Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans}, elocation-id = {131326}, year = {2017}, doi = {10.1101/131326}, publisher = {Cold Spring Harbor Laboratory}, abstract = {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.}, URL = {https://www.biorxiv.org/content/early/2017/04/26/131326}, eprint = {https://www.biorxiv.org/content/early/2017/04/26/131326.full.pdf}, journal = {bioRxiv} }