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Y-P30 promotes axonal growth by stabilizing growth cones.

Title: Y-P30 promotes axonal growth by stabilizing growth cones.
Authors: Neumann JR; AG Entwicklungsneurobiologie, Fakultät für Biologie und Biotechnologie, ND 6/72, Ruhr-Universität, 44801, Bochum, Germany.; Dash-Wagh S; Jüngling K; Tsai T; Meschkat M; Räk A; Schönfelder S; Riedel C; Hamad MI; Wiese S; Pape HC; Gottmann K; Kreutz MR; Wahle P
Source: Brain structure & function [Brain Struct Funct] 2015 Jul; Vol. 220 (4), pp. 1935-50. Date of Electronic Publication: 2014 Apr 13.
Publication Type: Journal Article; Research Support, Non-U.S. Gov't
Language: English
Journal Info: Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 101282001 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1863-2661 (Electronic) Linking ISSN: 18632653 NLM ISO Abbreviation: Brain Struct Funct Subsets: MEDLINE
Imprint Name(s): Original Publication: Berlin : Springer-Verlag, c2007-
MeSH Terms: Axons/*drug effects ; Growth Cones/*drug effects ; Neural Stem Cells/*drug effects ; Neurons/*cytology ; Peptides/*pharmacology; Actins/metabolism ; Cell Proliferation/drug effects ; Cerebral Cortex/cytology ; Cerebral Cortex/drug effects ; GAP-43 Protein/metabolism ; Gene Expression Regulation/drug effects ; MAP Kinase Signaling System/drug effects ; Neurons/drug effects ; Retina/cytology ; Retina/drug effects ; Semaphorin-3A/metabolism ; Animals ; Cells, Cultured ; Dose-Response Relationship, Drug ; Embryo, Mammalian ; Mice ; Molecular Imaging ; Organ Culture Techniques ; Rats ; Rats, Long-Evans
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.
Substance Nomenclature: 0 (Actins); 0 (GAP-43 Protein); 0 (Peptides); 0 (Semaphorin-3A); 0 (dermcidin)
Entry Date(s): Date Created: 20140415 Date Completed: 20160318 Latest Revision: 20150626
Update Code: 20260130
DOI: 10.1007/s00429-014-0764-2
PMID: 24728870
Database: MEDLINE

Journal Article; Research Support, Non-U.S. Gov't