title: Y-P30 promotes axonal growth by stabilizing growth cones.
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.
authors.affiliation: AG Entwicklungsneurobiologie, Fakultät für Biologie und Biotechnologie, ND 6/72, Ruhr-Universität, 44801, Bochum, Germany.
authors.forename: Janine R
authors.initials: JR
authors.lastname: Neumann
authors.forename: Suvarna
authors.initials: S
authors.lastname: Dash-Wagh
authors.forename: Kay
authors.initials: K
authors.lastname: Jüngling
authors.forename: Teresa
authors.initials: T
authors.lastname: Tsai
authors.forename: Martin
authors.initials: M
authors.lastname: Meschkat
authors.forename: Andrea
authors.initials: A
authors.lastname: Räk
authors.forename: Sabine
authors.initials: S
authors.lastname: Schönfelder
authors.forename: Christian
authors.initials: C
authors.lastname: Riedel
authors.forename: Mohammad I K
authors.initials: MI
authors.lastname: Hamad
authors.forename: Stefan
authors.initials: S
authors.lastname: Wiese
authors.forename: Hans-Christian
authors.initials: HC
authors.lastname: Pape
authors.forename: Kurt
authors.initials: K
authors.lastname: Gottmann
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kreutz
authors.forename: Petra
authors.initials: P
authors.lastname: Wahle
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004622:Embryo, Mammalian; D019922:GAP-43 Protein / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D020439:Growth Cones / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D051379:Mice; D057054:Molecular Imaging; D058953:Neural Stem Cells / Q000187:drug effects*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology*; D051381:Rats; D020318:Rats, Long-Evans; D012160:Retina / Q000166:cytology / Q000187:drug effects; D040121:Semaphorin-3A / Q000378:metabolism
chemical_list: D000199:Actins; D019922:GAP-43 Protein; D010455:Peptides; D040121:Semaphorin-3A; C442243:dermcidin