Ruhr-Universität Bochum, AG Entwicklungsneurobiologie, Fakultät für Biologie und Biotechnologie, Bochum, Germany.
Institut für Physiologie I, Westfälische Wilhelms-Universität Münster, Münster, Germany.
PLoS One. 2019 Feb 13;14(2):e0211151. doi: 10.1371/journal.pone.0211151. eCollection 2019.
The 30-amino acid peptide Y-P30 corresponds to the N-terminus of the primate-specific, sweat gland-derived dermcidin prepropeptide. Previous work has revealed that Y-P30 enhances the interaction of pleiotrophin and syndecans-2/3, and thus represents a natural ligand to study this signaling pathway. In immature neurons, Y-P30 activates the c-Src and p42/44 ERK kinase pathway, increases the amount of F-actin in axonal growth cones, and promotes neuronal survival, cell migration and axonal elongation. The action of Y-P30 on axonal growth requires syndecan-3 and heparan sulfate side chains. Whether Y-P30 has the potential to influence dendrites and dendritic protrusions has not been explored. The latter is suggested by the observations that syndecan-2 expression increases during postnatal development, that syndecan-2 becomes enriched in dendritic spines, and that overexpression of syndecan-2 in immature neurons results in a premature morphological maturation of dendritic spines. Here, analysing rat cortical pyramidal and non-pyramidal neurons in organotypic cultures, we show that Y-P30 does not alter the development of the dendritic arborization patterns. However, Y-P30 treatment decreases the density of apical, but not basal dendritic protrusions at the expense of the filopodia. Analysis of spine morphology revealed an unchanged mushroom/stubby-to-thin spine ratio and a shortening of the longest decile of dendritic protrusions. Whole-cell recordings from cortical principal neurons in dissociated cultures grown in the presence of Y-P30 demonstrated a decrease in the frequency of glutamatergic mEPSCs. Despite these differences in protrusion morphology and synaptic transmission, the latter likely attributable to presynaptic effects, calcium event rate and amplitude recorded in pyramidal neurons in organotypic cultures were not altered by Y-P30 treatment. Together, our data suggest that Y-P30 has the capacity to decelerate spinogenesis and to promote morphological, but not synaptic, maturation of dendritic protrusions.
30 个氨基酸的肽 Y-P30 对应于灵长类特有的、汗腺衍生的 dermcidin 前肽的 N 端。先前的工作表明，Y-P30 增强了多效蛋白和 syndecans-2/3 的相互作用，因此代表了研究这种信号通路的天然配体。在未成熟的神经元中，Y-P30 激活 c-Src 和 p42/44 ERK 激酶途径，增加轴突生长锥中的 F-肌动蛋白量，并促进神经元存活、细胞迁移和轴突伸长。Y-P30 对轴突生长的作用需要 syndecan-3 和肝素硫酸盐侧链。Y-P30 是否有可能影响树突和树突突起尚未被探索。 syndecan-2 的表达在出生后发育过程中增加，syndecan-2 在树突棘中富集，以及在未成熟神经元中过表达 syndecan-2 导致树突棘的过早形态成熟，这表明了这一点。在这里，我们在器官型培养物中分析大鼠皮质锥体细胞和非锥体细胞，结果表明 Y-P30 不会改变树突分支模式的发育。然而，Y-P30 处理会减少顶端但不减少基底树突突起的密度，代价是丝状伪足。对棘突形态的分析显示蘑菇/短棘-细长棘的比例不变，最长十分位数的树突突起缩短。在存在 Y-P30 的情况下培养的分离培养的皮质主神经元的全细胞记录显示谷氨酸能 mEPSC 的频率降低。尽管在突起形态和突触传递方面存在差异，但后者可能归因于突触前效应，器官型培养物中的锥体细胞记录的钙事件率和幅度不受 Y-P30 处理的影响。总之，我们的数据表明，Y-P30 有能力减缓 spinogenesis 并促进树突突起的形态但不是突触成熟。
