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Title: Schwann cell-specific PTEN and EGFR dysfunctions affect neuromuscular junction development by impairing Agrin signalingand autophagy
Authors: Zhang, SJ 
Li, XX 
Yu, Y 
Chiu, AP 
Lo, LH 
To, JC 
Rowlands, DK
Keng, VW 
Issue Date: 12-Jul-2019
Source: Biochemical and biophysical research communications, 12 Jul 2019, v. 515, no. 1, p. 50-56
Abstract: 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; Ptenflox/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.
Keywords: Neuromuscular junction
Schwann cells
Pten
EGFR
Publisher: Elsevier
Journal: Biochemical and biophysical research communications 
ISSN: 0006-291X
EISSN: 1090-2104
DOI: 10.1016/j.bbrc.2019.05.014
Rights: © 2019 Elsevier Inc. All rights reserved.
© 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/.
The following publication Zhang, S.-J., Li, X.-X., Yu, Y., Chiu, A. P., Lo, L. H., To, J. C., . . . Keng, V. 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), 50-56 is available at https://dx.doi.org/10.1016/j.bbrc.2019.05.014
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