Y-P30 promotes axonal growth by stabilizing growth cones

• Published in: Brain Structure and Function 2015-07, Vol.220 (4), p.1935-1950
• Main Authors: Neumann, Janine R., Dash-Wagh, Suvarna, Jüngling, Kay, Tsai, Teresa, Meschkat, Martin, Räk, Andrea, Schönfelder, Sabine, Riedel, Christian, Hamad, Mohammad I. K., Wiese, Stefan, Pape, Hans-Christian, Gottmann, Kurt, Kreutz, Michael R., Wahle, Petra
• Format: Article
• Language: English
• Subjects: Actins - metabolism; Amino acids; Animals; Axons - drug effects; Biomedical and Life Sciences; Biomedicine; Cell Biology; Cell Proliferation - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Cerebral Cortex - drug effects; Dose-Response Relationship, Drug; Embryo, Mammalian; GAP-43 Protein - metabolism; Gene Expression Regulation - drug effects; Growth Cones - drug effects; MAP Kinase Signaling System - drug effects; Mice; Molecular Imaging; Neural Stem Cells - drug effects; Neurology; Neurons; Neurons - cytology; Neurons - drug effects; Neurosciences; Organ Culture Techniques; Original Article; Peptides; Peptides - pharmacology; Proteins; Rats; Rats, Long-Evans; Retina; Retina - cytology; Retina - drug effects; Semaphorin-3A - metabolism; Spinal cord
• ISSN: 1863-2653; 1863-2661; 0340-2061
• DOI: 10.1007/s00429-014-0764-2

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.