ENA/VASP downregulation triggers cell death by impairing axonal maintenance in hippocampal neurons

Research output: Contribution to journalArticlepeer-review

Authors

  • D. Lorena Franco
  • Carolina Rezaval
  • Alfredo Cáceres
  • Alejandro F. Schinder
  • M. Fernanda Ceriani

Colleges, School and Institutes

Abstract

Neurodegenerative diseases encompass a broad variety of motor and cognitive disorders that are accompanied by death of specific neuronal populations or brain regions. Cellular and molecular mechanisms underlying these complex disorders remain largely unknown. In a previous work we searched for novel Drosophila genes relevant for neurodegeneration and singled out enabled (ena), which encodes a protein involved in cytoskeleton remodeling. To extend our understanding on the mechanisms of ENA-triggered degeneration we now investigated the effect of silencing ena ortholog genes in mouse hippocampal neurons. We found that ENA/VASP downregulation led to neurite retraction and concomitant neuronal cell death through an apoptotic pathway. Remarkably, this retraction initially affected the axonal structure, showing no effect on dendrites. Reduction in ENA/VASP levels blocked the neuritogenic effect of a specific RhoA kinase (ROCK) inhibitor, thus suggesting that these proteins could participate in the Rho-signaling pathway. Altogether these observations demonstrate that ENA/VASP proteins are implicated in the establishment and maintenance of the axonal structure and that a change on their expression levels triggers neuronal degeneration.

Details

Original languageEnglish
Pages (from-to)154-164
Number of pages11
JournalMolecular and Cellular Neuroscience
Volume44
Issue number2
Early online date15 Mar 2010
Publication statusPublished - 1 Jun 2010