A tubulin-MAPKKK pathway engages tubulin isotype interaction for neuroprotection

• 成果类型: Article
• 署名作者: Zhou, Junxiang; Feng, Chihin; Sun, Yue; Noma, Kentaro; Jin, Yishi
• 署名单位: University of California System; University of California San Diego; Nagoya University
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-13772
• DOI: 10.1073/pnas.2507208122
• 发表日期: 2025-08-26
• 关键词: alpha-beta-tubulin; microtubule dynamics; binding proteins; self-repair; mutations; expression; STABILITY; transport; neurons; GROWTH

摘要

The microtubule (MT) cytoskeleton is essential for neuronal morphology, neurite growth, synapse formation and maintenance, as well as regulation of signal transduction. Most cells express multiple isotypes of alpha- and beta-tubulin that can coassemble into MTs. While a variety of signaling pathways regulate MT integrity and homeostasis, little is known about how tubulin isotypes interact in vivo. Here, we report a mechanism in conserved kinase DLK-1 and its downstream signal transduction, which in turn upregulates expression of an alpha-tubulin isotype to ensure MT integrity. We find that alteraislands along MTs in neurites. Combining genome editing with cellular imaging, we identified amino acid residues in alpha-tubulin/TBA-2 that are necessary for formation transcription and protects axon and synapse morphology. These data uncover a posimaintains neuronal resilience.