TY - JOUR
T1 - Y-P30 promotes axonal growth by stabilizing growth cones
AU - Neumann, Janine R.
AU - Dash-Wagh, Suvarna
AU - Jüngling, Kay
AU - Tsai, Teresa
AU - Meschkat, Martin
AU - Räk, Andrea
AU - Schönfelder, Sabine
AU - Riedel, Christian
AU - Hamad, Mohammad I.K.
AU - Wiese, Stefan
AU - Pape, Hans Christian
AU - Gottmann, Kurt
AU - Kreutz, Michael R.
AU - Wahle, Petra
N1 - Publisher Copyright:
© 2014, Springer-Verlag Berlin Heidelberg.
PY - 2015/7/27
Y1 - 2015/7/27
N2 - 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.
AB - 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.
KW - Cortex
KW - Pleiotrophin
KW - Retina
KW - Spinal cord
KW - Syndecan
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UR - http://www.scopus.com/inward/citedby.url?scp=84933182293&partnerID=8YFLogxK
U2 - 10.1007/s00429-014-0764-2
DO - 10.1007/s00429-014-0764-2
M3 - Article
C2 - 24728870
AN - SCOPUS:84933182293
SN - 1863-2653
VL - 220
SP - 1935
EP - 1950
JO - Brain Structure and Function
JF - Brain Structure and Function
IS - 4
ER -