Neurons maintain axonal homeostasis via employing a unique organization of the microtubule (MT) cytoskeleton, which supports axonal morphology and provides tracks for intracellular transport. Abnormal MT-based trafficking hallmarks the pathology of neurodegenerative diseases, but the exact mechanism regulating MT dynamics in axons remains enigmatic. Here we report on a regulation of MT dynamics by AuTophaGy(ATG)-related proteins, which previously have been linked to the autophagy pathway. We find that ATG proteins required for LC3 lipid conjugation are dispensable for survival of excitatory neurons and instead regulate MT stability via controlling the abundance of the MT-binding protein CLASP2. This function of ATGs is independent of their role in autophagy and requires the active zone protein ELKS1. Our results highlight a non-canonical role of ATG proteins in neurons and suggest that pharmacological activation of autophagy may not only promote the degradation of cytoplasmic material, but also impair axonal integrity via altering MT stability.

神经元通过采用微管（MT）细胞骨架的独特组织来维持轴突的稳态，该组织支持轴突的形态并提供细胞内运输的轨迹。基于MT的异常贩运是神经退行性疾病的病理特征，但是调节轴突中MT动态的确切机制仍然是个谜。在这里，我们报告了AuTophaGy（ATG）相关蛋白对MT动力学的调节，该蛋白先前已与自噬途径相关。我们发现，LC3脂质结合所需的ATG蛋白对于兴奋性神经元的生存是必不可少的，而是通过控制MT结合蛋白CLASP2的丰度来调节MT的稳定性。ATG的功能与其在自噬中的作用无关，并且需要活性区蛋白ELKS1。