机构：[1]Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China[2]Department of Neurology, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China广东省中医院[3]Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China[4]Laboratory Animal Services Centre, The Chinese University of Hong Kong, Sha Tin, New Territories, Hong Kong SAR, China
The neuromuscular junction (NMJ) is formed by motor nerve terminals, post-junctional muscle membranes, and terminal Schwann cells (SCs). The formation of NMJ requires complex and dynamic molecular interactions. Nerve- and muscle-derived molecules have been well characterized but the mechanistic involvement of SC in NMJ development remains poorly understood. SC-specific phosphatase and tensin homolog (Pten) inactivation and epidermal growth factor receptor (EGFR) overexpression (Dhh-Cre; Cnp-EGFR; Pten(flox/flox) or DET) mice were used and NMJ malformation was observed in these mice. Acetylcholine receptors (AChRs) were distorted and varicose presynaptic nerve terminals appeared in the tibialis anterior (TA) muscle of DET mice. Agrin signaling related to NMJ development, was downregulated in TA muscle. Both RAS/mEK/ERK and PI3K/AKT/mTOR signaling pathways were activated in the sciatic nerves of DET mice. In addition, autophagy was downregulated in these sciatic nerves. Interestingly, the use of Torin 2, an mTOR inhibitor, rescued the phenotype. The downregulated-autophagy might account for Agrin signaling abnormity, which induced NMJ malformation. Taken together, our results indicate that SCs-specific Pten and EGFR cooperation are essential for NMJ development. (C) 2019 Elsevier Inc, All rights reserved.
基金：
Research Grants Council Collaborative Research Fund Scheme, Hong Kong SAR Government [C5012-15E]; Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong SAR (G-YBTA)
第一作者机构：[1]Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Kowloon, Hong Kong SAR, China[2]Department of Neurology, Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China[3]Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China
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推荐引用方式(GB/T 7714)：
Zhang Shi-Jie,Li Xiao-Xiao,Yu Yuyu,et al.Schwann cell-specific PTEN and EGFR dysfunctions affect neuromuscular junction development by impairing Agrin signaling and autophagy[J].BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS.2019,515(1):50-56.doi:10.1016/j.bbrc.2019.05.014.
APA：
Zhang, Shi-Jie,Li, Xiao-Xiao,Yu, Yuyu,Chiu, Amy P.,Lo, Lilian H....&Keng, Vincent W..(2019).Schwann cell-specific PTEN and EGFR dysfunctions affect neuromuscular junction development by impairing Agrin signaling and autophagy.BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS,515,(1)
MLA：
Zhang, Shi-Jie,et al."Schwann cell-specific PTEN and EGFR dysfunctions affect neuromuscular junction development by impairing Agrin signaling and autophagy".BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 515..1(2019):50-56
