ABSTRACT
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.
Subject(s)
Autophagy/physiology , Axons/physiology , Lipid Metabolism/physiology , Microtubules/metabolism , Animals , Animals, Newborn , Autophagy-Related Protein 5/genetics , Autophagy-Related Protein 5/metabolism , Cell Survival , Cells, Cultured , Gene Knockout Techniques , Mice , Microtubule-Associated Proteins/genetics , Microtubule-Associated Proteins/metabolism , Nerve Tissue Proteins/metabolism , Primary Cell Culture , Recombinant Proteins/genetics , Recombinant Proteins/metabolism , rab GTP-Binding Proteins/metabolismABSTRACT
Presence of GABA-immunoreactive fibres in the nerve cervicalis inferior was shown as well as their regulatory effects upon contractions of the dorsal longitudinal muscle in Lymnaea stagnalis. The exogenous GABA affected the amplitude of evoked muscle contractions diminishing them at concentrations from 10(-8) M and augmenting them from above 10(-5) M. Picrotoxin produced opposite effects on the muscle contractions in the same concentration range. Bicucullin did not affect the contractions. The findings are discussed from the standpoint of the supposed functional heterogeneity of the GABA receptors in the mollusc nerve-muscle junction.
