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The netrin-1 receptor DCC promotes filopodia formation and cell spreading by activating Cdc42 and Rac1

Masoud Shekarabi1, Timothy E Kennedy

  • 1Centre for Neuronal Survival, McGill University, Montreal, Quebec, H3A 2B4, Canada.

Molecular and Cellular Neurosciences
|January 31, 2002
PubMed

Insights

Netrin-1 signaling through its receptor, deleted in colorectal cancer (DCC), regulates cell motility. This interaction activates Cdc42 and Rac1, influencing actin-based membrane extensions during neural development.

Area of Science:

  • Neuroscience
  • Cell Biology
  • Molecular Biology

Background:

  • Netrins are secreted proteins crucial for neural development, guiding cell and axon migration.
  • The netrin-1 receptor, deleted in colorectal cancer (DCC), plays a role in cellular processes.
  • Understanding the precise function of DCC in neuronal development is essential.

Purpose of the Study:

  • To investigate the role of the netrin-1 receptor (DCC) in cellular motility.
  • To characterize the expression of netrins and netrin receptors in cell lines.
  • To elucidate the downstream signaling pathways activated by netrin-1/DCC interaction.

Main Methods:

  • Expression analysis of netrins and netrin receptors in HEK293T and NG108-15 cells.
  • Ectopic expression of DCC in cells lacking endogenous expression.
  • Functional assays involving dominant-negative Cdc42 and Rac1 to assess filopodia formation and cell surface area.
  • Measurement of Cdc42 and Rac1 activation upon netrin-1 stimulation.

Main Results:

  • Netrin-1 was expressed in HEK293T and NG108-15 cells, but DCC was absent.
  • Ectopic DCC expression led to a netrin-1-dependent increase in filopodia and cell surface area.
  • Inhibition of Cdc42 or Rac1 blocked DCC-mediated increases in filopodia and cell surface area, respectively.
  • Netrin-1 induced persistent activation of Cdc42 and Rac1 in DCC-expressing cells.

Conclusions:

  • Netrin-1, acting through DCC, modulates cellular motility.
  • The netrin-1/DCC pathway regulates actin-based membrane extensions via Cdc42 and Rac1 activation.
  • This signaling mechanism is important for cellular migration during neural development.

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