Neuronal gelsolin prevents apoptosis by enhancing actin depolymerization

Christoph Harms, Julian Bösel, Marion Lautenschlager, Ulrike Harms, Johann S. Braun, Heide Hörtnagl, Ulrich Dirnagl, David J. Kwiatkowski, Klaus Fink, Matthias Endres

Research output: Contribution to journalArticlepeer-review

72 Citations (Scopus)


Gelsolin (gsn), an actin-severing protein, protects neurons from excitotoxic cell death via inactivation of membranous Ca2+ channels. Its role during apoptotic cell death, however, has remained unclear. Using several models of neuronal cell death, we demonstrate that endogenous gelsolin has anti-apoptotic properties that correlate to its dynamic actions on the cytoskeleton. We show that neurons lacking gelsolin (gsn-/-) have enhanced apoptosis following exposure to staurosporine, thapsigargin, or the cholinergic toxin ethylcholine aziridinium (AF64A). AF64A-induced loss of mitochondrial membrane potential and activation of caspase-3 was specifically enhanced in gsn-/- neurons and could be reversed by pharmacological inhibition of mitochondrial permeability transition. Moreover, increased caspase-3 activation and cell death in AF64A-treated gsn-/- neurons were completely reversed by pharmacological depolymerization of actin filaments and further enhanced by their stabilization. In conclusion, actin remodeling by endogenous gelsolin or analogues protects neurons from apoptosis mediated by mitochondria and caspase-3.

Original languageEnglish
Pages (from-to)69-82
Number of pages14
JournalMolecular and Cellular Neuroscience
Issue number1
Publication statusPublished - Jan 2004
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology


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