Remodeling of the Actin/Spectrin Membrane-associated Periodic Skeleton, Growth Cone Collapse and F-Actin Decrease during Axonal Degeneration

NICOLAS UNSAIN; MARTIN D BORDENAVE; GABY F MARTINEZ; SAMI JALIL; CATALINA VON BILDERLING; FEDERICO M BARABAS; LUCIANO MASULLO; AARON D JOHNSTONE; PHIL A BARKER ; MARIANO BISBAL; FERNANDO D STEFANI; ALFREDO CACERES

Scientific Reports

Nature Publishing Group

Año: 2018

Axonal degeneration occurs in the developing nervous system for the appropriateestablishment of mature circuits, and is also a hallmark of diverse neurodegenerative diseases. Despite recent interest in the field, little is known about the changes (and possible role) of the cytoskeleton during axonal degeneration. We studied the actin cytoskeleton in an in vitro model of developmental pruning induced by trophic factor withdrawal (TFW). We found that F-actin decreases and growth cone collapse (GCC) occurs early after TFW; however, treatments that prevent axonal fragmentation failed to prevent GCC, suggesting independent pathways. Using super-resolution (STED) microscopy we found that the axonal actin/spectrin membrane-associated periodic skeleton (MPS) abundance and organization drop shortly after deprivation, remaining low until fragmentation. Fragmented axons lack MPS (while maintaining microtubules) and acute pharmacological treatments that stabilize actin filaments prevent MPS loss and protect from axonal fragmentation, suggesting that MPS destruction is required for axon fragmentation to proceed.