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

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

Scientific Reports

Nature Publishing Group

Año: 2018 vol. 8

Axonal degeneration occurs in the developing nervous system for the appropriate establishment ofmature circuits, and is also a hallmark of diverse neurodegenerative diseases. Despite recent interestin the feld, little is known about the changes (and possible role) of the cytoskeleton during axonaldegeneration. We studied the actin cytoskeleton in an in vitro model of developmental pruning inducedby trophic factor withdrawal (TFW). We found that F-actin decrease and growth cone collapse (GCC)occur early after TFW; however, treatments that prevent axonal fragmentation failed to preventGCC, suggesting independent pathways. Using super-resolution (STED) microscopy we found thatthe axonal actin/spectrin membrane-associated periodic skeleton (MPS) abundance and organizationdrop shortly after deprivation, remaining low until fragmentation. Fragmented axons lack MPS (whilemaintaining microtubules) and acute pharmacological treatments that stabilize actin flaments preventMPS loss and protect from axonal fragmentation, suggesting that MPS destruction is required for axonfragmentation to proceed.