RRC ID 51470
著者 Zheng C, Diaz-Cuadros M, Nguyen KCQ, Hall DH, Chalfie M.
タイトル Distinct effects of tubulin isotype mutations on neurite growth in Caenorhabditis elegans.
ジャーナル Mol Biol Cell
Abstract Tubulins, the building block of microtubules (MTs), play a critical role in both supporting and regulating neurite growth. Eukaryotic genomes contain multiple tubulin isotypes, and their missense mutations cause a range of neurodevelopmental defects. Using the Caenorhabditis elegans touch receptor neurons, we analyzed the effects of 67 tubulin missense mutations on neurite growth. Three types of mutations emerged: 1) loss-of-function mutations, which cause mild defects in neurite growth; 2) antimorphic mutations, which map to the GTP binding site and intradimer and interdimer interfaces, significantly reduce MT stability, and cause severe neurite growth defects; and 3) neomorphic mutations, which map to the exterior surface, increase MT stability, and cause ectopic neurite growth. Structure-function analysis reveals a causal relationship between tubulin structure and MT stability. This stability affects neuronal morphogenesis. As part of this analysis, we engineered several disease-associated human tubulin mutations into C. elegans genes and examined their impact on neuronal development at the cellular level. We also discovered an α-tubulin (TBA-7) that appears to destabilize MTs. Loss of TBA-7 led to the formation of hyperstable MTs and the generation of ectopic neurites; the lack of potential sites for polyamination and polyglutamination on TBA-7 may be responsible for this destabilization.
巻・号 28(21)
ページ 2786-2801
公開日 2017-10-15
DOI 10.1091/mbc.E17-06-0424
PII mbc.E17-06-0424
PMID 28835377
PMC PMC5638583
MeSH Amino Acid Sequence Animals Caenorhabditis elegans / growth & development* Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / chemistry Caenorhabditis elegans Proteins / genetics Caenorhabditis elegans Proteins / metabolism Humans Microtubules / genetics Microtubules / physiology Mutation Neurites / metabolism* Neurites / physiology* Neurogenesis Neurons / metabolism Protein Isoforms / genetics Tubulin / chemistry Tubulin / genetics* Tubulin / metabolism*
IF 3.791
引用数 7
リソース情報
線虫 tm2143 tm5083