Light-Mediated Kinetic Control Reveals the Temporal Effect of the Raf/MEK/ERK Pathway in PC12 Cell Neurite Outgrowth

Details

• Alternative Title:
  PLoS One
• Personal Author:
  Zhang, Kai ; Duan, Liting ; Ong, Qunxiang ; Lin, Ziliang ; Varman, Pooja Mahendra ; Sung, Kijung ; Cui, Bianxiao
• Description:
  It has been proposed that differential activation kinetics allows cells to use a common set of signaling pathways to specify distinct cellular outcomes. For example, nerve growth factor (NGF) and epidermal growth factor (EGF) induce different activation kinetics of the Raf/MEK/ERK signaling pathway and result in differentiation and proliferation, respectively. However, a direct and quantitative linkage between the temporal profile of Raf/MEK/ERK activation and the cellular outputs has not been established due to a lack of means to precisely perturb its signaling kinetics. Here, we construct a light-gated protein-protein interaction system to regulate the activation pattern of the Raf/MEK/ERK signaling pathway. Light-induced activation of the Raf/MEK/ERK cascade leads to significant neurite outgrowth in rat PC12 pheochromocytoma cell lines in the absence of growth factors. Compared with NGF stimulation, light stimulation induces longer but fewer neurites. Intermittent on/off illumination reveals that cells achieve maximum neurite outgrowth if the off-time duration per cycle is shorter than 45 min. Overall, light-mediated kinetic control enables precise dissection of the temporal dimension within the intracellular signal transduction network.
• Subjects:
  Animals Cell Differentiation Cell Membrane Cryptochromes Dose-Response Relationship, Radiation Enzyme Activation Extracellular Signal-Regulated MAP Kinases Kinetics Light MAP Kinase Kinase Kinases MAP Kinase Signaling System Mice Nerve Growth Factor Neurites NIH 3T3 Cells PC12 Cells Protein Structure, Tertiary Protein Transport Raf Kinases Rats

  More +
• Source:
  PLoS One. 2014; 9(3).
• Pubmed ID:
  24667437
• Pubmed Central ID:
  PMC3965503
• Document Type:
  Journal Article
• Funding:
  DP2-NS082125/DP/NCCDPHP CDC HHS/United States
• Volume:
  9
• Issue:
  3
• Collection(s):
  CDC Public Access
• Main Document Checksum:
  urn:sha256:00010abb02df853243b542aa96db21eae6bf2d8e6ff9678ec9b744725b933944
• Download URL:
  https://stacks.cdc.gov/view/cdc/23146/cdc_23146_DS1.pdf
• File Type:
  [PDF - 3.86 MB ]