Taxol and tau overexpression induced calpain-dependent degradation of the microtubule-destabilizing protein SCG10

Irving E. Vega, Tadanori Hamano, Josh A. Propost, Gabriele Grenningloh, Shu Hui Yen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Microtubule-stabilizing and -destabilizing proteins play a crucial role in regulating the dynamic instability of microtubules during neuronal development and synaptic transmission. The microtubule-destabilizing protein SCG10 is a neuron-specific protein implicated in neurite outgrowth. The SCG10 protein is significantly reduced in mature neurons, suggesting that its expression is developmentally regulated. In contrast, the microtubule-stabilizing protein tau is expressed in mature neurons and its function is essential for the maintenance of neuronal polarity and neuronal survival. Thus, the establishment and maintenance of neuronal polarity may down-regulate the protein level/function of SCG10. In this report, we show that treatment of PC12 cells and neuroblastoma cells with the microtubule-stabilizing drug Taxol induced a rapid degradation of the SCG10 protein. Consistently, overexpression of tau protein in neuroblastoma cells also induced a reduction in SCG10 protein levels. Calpain inhibitor MDL-28170, but not caspase inhibitors, blocked a significant decrease in SCG10 protein levels. Collectively, these results indicate that tau overexpression and Taxol treatment induced a calpain-dependent degradation of the microtubule-destabilizing protein SCG10. The results provide evidence for the existence of an intracellular mechanism involved in the regulation of SCG10 upon microtubule stabilization.

Original languageEnglish (US)
Pages (from-to)152-160
Number of pages9
JournalExperimental Neurology
Volume202
Issue number1
DOIs
StatePublished - Nov 2006

Fingerprint

Microtubule Proteins
Calpain
Paclitaxel
Microtubules
Proteins
Neuroblastoma
Neurons
Maintenance
tau Proteins
Caspase Inhibitors
PC12 Cells
Synaptic Transmission
Proteolysis
Down-Regulation
Pharmaceutical Preparations

Keywords

  • Calpain
  • Degradation
  • Microtubules
  • SCG10
  • Tau
  • Taxol

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

Cite this

Taxol and tau overexpression induced calpain-dependent degradation of the microtubule-destabilizing protein SCG10. / Vega, Irving E.; Hamano, Tadanori; Propost, Josh A.; Grenningloh, Gabriele; Yen, Shu Hui.

In: Experimental Neurology, Vol. 202, No. 1, 11.2006, p. 152-160.

Research output: Contribution to journalArticle

Vega, Irving E. ; Hamano, Tadanori ; Propost, Josh A. ; Grenningloh, Gabriele ; Yen, Shu Hui. / Taxol and tau overexpression induced calpain-dependent degradation of the microtubule-destabilizing protein SCG10. In: Experimental Neurology. 2006 ; Vol. 202, No. 1. pp. 152-160.
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