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Mouse semaphorin H induces PC12 cell neurite outgrowth activating Ras-mitogen-activated protein kinase signaling

T Sakai1, T Furuyama, Y Ohoka

  • 1Group of Neurobiology, School of Allied Health Sciences, Osaka University Faculty of Medicine, Yamadaoka 1-7, Suita-shi, Osaka, 565-0871, Japan.

The Journal of Biological Chemistry
|October 9, 1999
PubMed

Insights

Mouse semaphorin H (MSH) promotes neurite outgrowth in PC12 cells. This process involves calcium influx and the Ras-MAPK pathway, distinct from nerve growth factor (NGF) signaling.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Mouse semaphorin H (MSH) is a secreted molecule previously identified as a chemorepulsive factor for sensory neurites.
  • Understanding the molecular mechanisms regulating neurite outgrowth is crucial for neural development and regeneration.

Purpose of the Study:

  • To investigate the role of mouse semaphorin H (MSH) in inducing neurite outgrowth in PC12 cells.
  • To elucidate the signaling pathways involved in MSH-mediated neurite outgrowth and compare them with nerve growth factor (NGF) signaling.

Main Methods:

  • PC12 cells were treated with varying concentrations of MSH to assess neurite outgrowth.
  • Ras-mitogen-activated protein kinase (MAPK) signaling pathways were analyzed.
  • The effects of tyrosine kinase receptor (Trk) inhibitors (K-252a) and voltage-dependent calcium channel blockers (diltiazem, omega-conotoxin) were evaluated.
  • Intracellular calcium levels were measured upon MSH stimulation.

Main Results:

  • MSH induced dose-dependent neurite outgrowth in PC12 cells.
  • The Ras-MAPK pathway was essential for MSH-induced neurite outgrowth, similar to NGF.
  • MSH action did not involve tyrosine kinase receptors (Trks), indicating a different receptor mechanism than NGF.
  • Calcium channel blockers inhibited MSH-induced neurite outgrowth and MAPK phosphorylation, demonstrating a Ca(2+)-dependent mechanism.
  • MSH stimulation led to a transient increase in intracellular Ca(2+) levels.

Conclusions:

  • MSH promotes neurite outgrowth in PC12 cells through a mechanism distinct from NGF.
  • Extracellular calcium influx is a critical step, activating the Ras-MAPK signaling pathway for MSH-induced neurite outgrowth.

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