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

• Published in: Scientific Reports
• Main Authors: Unsain, Nicolas, Bordenave, Martín Diego, Martinez, Gaby F., Jalil, Sami, Von Bilderling, Catalina, Barabas, Federico Martín, Masullo, Luciano Andrés, Johnstone, Aaron D., Barker, Philip A., Bisbal, Mariano, Stefani, Fernando Daniel, Caceres, Alfredo Oscar
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Publishing Group
• Subjects: NANOSCOPY; AXON; DEGENERATION; NEURONS; https://purl.org/becyt/ford/1.6; https://purl.org/becyt/ford/1; Argentina; Gaby; sami
• Online Access: http://hdl.handle.net/11336/90541

Axonal degeneration occurs in the developing nervous system for the appropriate establishment 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 decrease and growth cone collapse (GCC) occur 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. Fil: Unsain, Nicolas. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina Fil: Bordenave, Martín Diego. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Bionanociencias "Elizabeth Jares Erijman"; Argentina Fil: Martinez, Gaby F. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra. Universidad Nacional de Córdoba. Instituto de Investigación Médica Mercedes y Martín Ferreyra; Argentina Fil: Jalil, Sami. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico ...