Taxol and tau overexpression induced calpain-dependent degradation of the microtubule-destabilizing protein SCG10.
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.
Vega
Irving E
IE
Department of Neuroscience, Mayo Clinic College of Medicine, Mayo Clinic Jacksonville, Birdsall Medical Research Bldg., 4500 San Pablo Road, Jacksonville, FL 32224, USA. irving_vega@uprrp.edu
Hamano
Tadanori
T
Propost
Josh A
JA
Grenningloh
Gabriele
G
Yen
Shu-Hui
SH
D000818:Animals; D015153:Blotting, Western / Q000379:methods; D002154:Calpain / Q000378:metabolism*; D002460:Cell Line; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism*; D009447:Neuroblastoma; D017239:Paclitaxel / Q000494:pharmacology*; D051381:Rats; D050777:Stathmin; D014162:Transfection / Q000379:methods; D050257:Tubulin Modulators / Q000494:pharmacology*; D016875:tau Proteins / Q000378:metabolism*
D015853:Cysteine Proteinase Inhibitors; D007976:Leupeptins; D008565:Membrane Proteins; C063314:STMN2 protein, human; D050777:Stathmin; D050257:Tubulin Modulators; D016875:tau Proteins; D002154:Calpain; D017239:Paclitaxel; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde