Tropomodulins are negative regulators of neurite outgrowth

Thomas Fath*, Robert S. Fischer, Leif Dehmelt, Shelley Halpain, Velia M. Fowler

*Corresponding author for this work

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Regulation of the actin cytoskeleton is critical for neurite formation. Tropomodulins (Tmods) regulate polymerization at actin filament pointed ends. Previous experiments using a mouse model deficient for the neuron specific isoform Tmod2 suggested a role for Tmods in neuronal function by impacting processes underlying learning and memory. However, the role of Tmods in neuronal function on the cellular level remains unknown. Immunofluorescence localization of the neuronal isoforms Tmod1 and Tmod2 in cultured rat primary hippocampal neurons revealed that Tmod1 is enriched along the proximal part of F-actin bundles in lamellipodia of spreading cells and in growth cones of extending neurites, while Tmod2 appears largely cytoplasmic. Functional analysis of these Tmod isoforms in a mouse neuroblastoma N2a cell line showed that knockdown of Tmod2 resulted in a significant increase in the number of neurite-forming cells and in neurite length. While N2a cells compensated for Tmod2 knockdown by increasing Tmod1 levels, over-expression of exogenous Tmod1 had no effect on neurite outgrowth. Moreover, knockdown of Tmod1 increased the number of neurites formed per cell, without effect on the number of neurite-forming cells or neurite length. Taken together, these results indicate that Tmod1 and Tmod2 have mechanistically distinct inhibitory roles in neurite formation, likely mediated via different effects on F-actin dynamics and via differential localizations during early neuritogenesis.

Original languageEnglish
Pages (from-to)291-300
Number of pages10
JournalEuropean Journal of Cell Biology
Volume90
Issue number4
DOIs
Publication statusPublished - 1 Apr 2011
Externally publishedYes

Keywords

  • Cultured hippocampal neurons
  • F-actin
  • N2a mouse neuroblastoma cells
  • Neurite outgrowth
  • Tropomodulin

Fingerprint Dive into the research topics of 'Tropomodulins are negative regulators of neurite outgrowth'. Together they form a unique fingerprint.

Cite this