Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, 350, Taiwan.
Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, 807, Taiwan.
Sci Rep. 2017 Jul 12;7(1):5241. doi: 10.1038/s41598-017-05584-7.
Expression of neuroendocrine-associated phosphatase (NEAP, also named as dual specificity phosphatase 26, [DUSP26]) is restricted to neuroendocrine tissues. We found that NEAP, but not its phosphatase-defective mutant, suppressed nerve growth factor (NGF) receptor TrkA and fibroblast growth factor receptor 1 (FGFR1) activation in PC12 cells upon NGF stimulation. Conversely, suppressing NEAP expression by RNA interference enhanced TrkA and FGFR1 phosphorylation. NEAP was capable of de-phosphorylating TrkA and FGFR1 directly in vitro. NEAP-orthologous gene existed in zebrafish. Morpholino (MO) suppression of NEAP in zebrafish resulted in hyper-phosphorylation of TrkA and FGFR1 as well as abnormal body postures and small eyes. Differentiation of retina in zebrafishes with NEAP MO treatment was severely defective, so were cranial motor neurons. Taken together, our data indicated that NEAP/DUSP26 have a critical role in regulating TrkA and FGFR1 signaling as well as proper development of retina and neuronal system in zebrafish.
神经内分泌相关磷酸酶（NEAP，也称为双特异性磷酸酶 26，[DUSP26]）的表达仅限于神经内分泌组织。我们发现，在 NGF 刺激下，NEAP（而非其磷酸酶缺陷突变体）抑制 PC12 细胞中神经生长因子（NGF）受体 TrkA 和成纤维细胞生长因子受体 1（FGFR1）的激活。相反，通过 RNA 干扰抑制 NEAP 的表达增强了 TrkA 和 FGFR1 的磷酸化。NEAP 能够在体外直接去磷酸化 TrkA 和 FGFR1。斑马鱼中存在与 NEAP 同源的基因。用 NEAP 的 morpholino（MO）抑制斑马鱼中的 NEAP 导致 TrkA 和 FGFR1 的过度磷酸化，以及异常的身体姿势和小眼睛。用 NEAP MO 处理的斑马鱼视网膜分化严重缺陷，颅运动神经元也是如此。总之，我们的数据表明，NEAP/DUSP26 在调节 TrkA 和 FGFR1 信号以及斑马鱼视网膜和神经元系统的正常发育中起着关键作用。
