Y-P30 promotes axonal growth by stabilizing growth cones

Janine R. Neumann, Suvarna Dash-Wagh, Kay Jüngling, Teresa Tsai, Martin Meschkat, Andrea Räk, Sabine Schönfelder, Christian Riedel, Mohammad I.K. Hamad, Stefan Wiese, Hans Christian Pape, Kurt Gottmann, Michael R. Kreutz, Petra Wahle

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

The 30-amino acid peptide Y-P30, generated from the N-terminus of the human dermcidin precursor protein, has been found to promote neuronal survival, cell migration and neurite outgrowth by enhancing the interaction of pleiotrophin and syndecan-3. We now show that Y-P30 activates Src kinase and extracellular signal-regulated kinase (ERK). Y-P30 promotes axonal growth of mouse embryonic stem cell-derived neurons, embryonic mouse spinal cord motoneurons, perinatal rat retinal neurons, and rat cortical neurons. Y-P30-mediated axon growth was dependent on heparan sulfate chains. Y-P30 decreased the proportion of collapsing/degenerating growth cones of cortical axons in an Src and ERK-dependent manner. Y-P30 increased for 90 min in axonal growth cones the level of Tyr418-phosphorylated Src kinase and the amount of F-actin, and transiently the level of Tyr-phosphorylated ERK. Levels of total Src kinase, actin, GAP-43, cortactin and the glutamate receptor subunit GluN2B were not altered. When exposed to semaphorin-3a, Y-P30 protected a significant fraction of growth cones of cortical neurons from collapse. These results suggest that Y-P30 promotes axonal growth via Src- and ERK-dependent mechanisms which stabilize growth cones and confer resistance to collapsing factors.

Original languageEnglish
Pages (from-to)1935-1950
Number of pages16
JournalBrain Structure and Function
Volume220
Issue number4
DOIs
Publication statusPublished - Jul 27 2015
Externally publishedYes

Keywords

  • Cortex
  • Pleiotrophin
  • Retina
  • Spinal cord
  • Syndecan

ASJC Scopus subject areas

  • Anatomy
  • General Neuroscience
  • Histology

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