Autophagy lipidation machinery regulates microtubule dynamics to maintain axonal homeostasis

ABSTRACT: Axon integrity is crucial for neuronal function. To maintain axonal homeostasis neurons have evolved a unique organization of the microtubule (MT) cytoskeleton, which supports axonal morphology and provides tracks for intracellular transport. Although abnormal MT-based trafficking highlights the pathology of neurodegenerative diseases, the exact mechanism regulating MT dynamics in the axon remains enigmatic. Here we report on a novel regulation of MT dynamics by autophagy, the pathway, which previously has been linked to lysosomal degradation. We find that AuTophaGy(ATG)-related proteins required for LC3 lipid conjugation regulate MT stability via controlling the abundance of MT-binding protein CLASP2. This function of ATGs is independent of their role in protein degradation and requires the active zone protein ELKS1. Our results highlight a novel role of autophagy in neurons and suggest that pharmacological activation of autophagy may not only promote the degradation of bulk cytoplasmic material, but also impair axonal integrity via altering the MT stability.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Christian Frese  

LAB HEAD: Christian Frese

PROVIDER: PXD011279 | Pride | 2020-03-25

REPOSITORIES: Pride