Y-P30 promotes axonal growth by stabilizing growth cones

• Autores: 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
• Localización: Brain Structure and Function, ISSN 1863-2653, ISSN-e 1863-2661, Vol. 220, Nº. 4, 2015, págs. 1935-1950
• Idioma: inglés
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• Resumen

  • 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.;