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Y-P30 promotes axonal growth by stabilizing growth cones

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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.

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Acknowledgments

Supported by Deutsche Forschungsgemeinschaft Graduiertenkolleg 736 (stipends to S.D.-W., J.R.N., M.I.K.H. and K.J.), Deutsche Forschungsgemeinschaft Sonderforschungsbereich 509 (TP C2 to P.W.), Bundesministerium für Bildung und Forschung (Förderschwerpunkt Neurotraumatologie, TP A11 to H.C.P. and P.W.), Leibniz Society (Pakt für Forschung to M.R.K.), Deutsche Forschungsgemeinschaft Sonderforschungsbereich 854 (TP7 to M.R.K.) and Stammzellnetzwerk Nordrhein-Westfalen (AZ 224-400 010 04 to P.W. and K.G). Mouse embryonic stem cell line D3 was a gift from Dr. Fleischmann, Department of Neurophysiology, Universität Köln, Germany, to K.J. and K.G.). TRITC-conjugated phalloidin was a gift of Dr. Melanie Mark, Department of Zoology and Neurobiology, Ruhr University.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. AG Entwicklungsneurobiologie, Fakultät für Biologie und Biotechnologie, ND 6/72, Ruhr-Universität, 44801, Bochum, Germany

    Janine R. Neumann, Suvarna Dash-Wagh, Martin Meschkat, Andrea Räk, Sabine Schönfelder, Christian Riedel, Mohammad I. K. Hamad & Petra Wahle

  2. AG Molekulare Zellbiologie, Fakultät für Biologie und Biotechnologie, Ruhr-Universität, 44801, Bochum, Germany

    Teresa Tsai & Stefan Wiese

  3. Institut für Neuro- und Sinnesphysiologie, Fakultät für Medizin, Heinrich Heine Universität, 40225, Düsseldorf, Germany

    Kay Jüngling & Kurt Gottmann

  4. Institut für Physiologie I, Westfälische Wilhelms-Universität, 48149, Münster, Germany

    Kay Jüngling & Hans-Christian Pape

  5. FG Neuroplastizität, Leibniz-Institut für Neurobiologie, 39118, Madgeburg, Germany

    Michael R. Kreutz

  6. AG Entwicklungsneurobiologie, Fakultät für Biologie und Biotechnologie, ND 6/72, Ruhr-Universität, 44780, Bochum, Germany

    Petra Wahle

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  1. Janine R. Neumann
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  2. Suvarna Dash-Wagh
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Correspondence to Petra Wahle.

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J. R. Neumann and S. Dash-Wagh share equal contribution authorship.

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Neumann, J.R., Dash-Wagh, S., Jüngling, K. et al. Y-P30 promotes axonal growth by stabilizing growth cones. Brain Struct Funct 220, 1935–1950 (2015). https://doi.org/10.1007/s00429-014-0764-2

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