Induction of CRMP-2 by GDNF and analysis of the CRMP-2 promoter region.
Collapsin response mediator protein-2 (CRMP-2) is a mammalian homologue of UNC-33 of Caenorhabditis elegans. Mutations of CRMP-2 result in abnormal axon termination. Recently, it was demonstrated that CRMP-2 binds to tubulin heterodimers to promote microtubule assembly that is critical for axonal differentiation and growth during development. Here we show that glial cell line-derived neurotrophic factor (GDNF) enhances CRMP-2 expression in TGW human neuroblastoma cells via activation of RET receptor tyrosine kinase. GDNF-mediated CRMP-2 expression was regulated mainly by the extracellular regulated kinase (ERK) pathway, but was independent of activation of phosphatidylinositol 3-kinase and Src family kinases. Analysis of the promoter region of the CRMP-2 gene revealed that the region 214-48 bp upstream of the transcriptional start site is important for CRMP-2 expression. The SP1, E2F, and GATA1/2 binding sites appeared to play some roles in regulation of CRMP-2 expression. As expected, the CRMP-2 protein accumulated in extended neurites of TGW cells treated with GDNF. However, neuritogenesis of TGW cells was mostly dependent on Src family kinase activity and not ERK activity, indicating that the increased expression of CRMP-2 alone was not sufficient for neuritogenesis.
Kodama
Yoshinori
Y
Department of Pathology, Nagoya University Graduate School of Medicine, Japan.
Murakumo
Yoshiki
Y
Ichihara
Masatoshi
M
Kawai
Kumi
K
Shimono
Yohei
Y
Takahashi
Masahide
M
D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects; D009447:Neuroblastoma / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects; D014018:Tissue Distribution
C495039:GDNF protein, human; D051100:Glial Cell Line-Derived Neurotrophic Factor; D036341:Intercellular Signaling Peptides and Proteins; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D020928:Mitogen-Activated Protein Kinases