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한빛사논문
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Proc. Natl. Acad. Sci. USA, Published online before print January 11, 2016 | doi: 10.1073/pnas.1519156113
Neuregulin1 displayed on motor axons regulates terminal Schwann cell-mediated synapse elimination at developing neuromuscular junctions
Abstract
Young il Leea,1, Yue Lib, Michelle Mikeshc, Ian Smithd, Klaus-Armin Navee, Markus H. Schwabf, and Wesley J. Thompsona,1
aDepartment of Biology, Texas A&M University, College Station, TX 77843;
bDell Pediatric Research Institute, The University of Texas, Austin, TX 78712;
cSection of Molecular Cell and Developmental Biology, The University of Texas, Austin, TX 78712;
dInstitute for Neuroscience, Texas A&M University, College Station, TX 77843;
eDepartment of Neurogenetics, Max Planck Institute of Experimental Medicine, 37075 Gottingen, Germany;
fDepartment of Cellular Neurophysiology, Hannover Medical School, 30625 Hannover, Germany
Abstract
Synaptic connections in the nervous system are rearranged during development and in adulthood as a feature of growth, plasticity, aging, and disease. Glia are implicated as active participants in these changes. Here we investigated a signal that controls the participation of peripheral glia, the terminal Schwann cells (SCs), at the neuromuscular junction (NMJ) in mice. Transgenic manipulation of the levels of membrane-tethered neuregulin1 (NRG1-III), a potent activator of SCs normally presented on motor axons, alters the rate of loss of motor inputs at NMJs during developmental synapse elimination. In addition, NMJs of adult transgenic mice that expressed excess axonal NRG1-III exhibited continued remodeling, in contrast to the more stable morphologies of controls. In fact, synaptic SCs of these adult mice with NRG1-III overexpression exhibited behaviors evident in wild type neonates during synapse elimination, including an affinity for the postsynaptic myofiber surface and phagocytosis of nerve terminals. Given that levels of NRG1-III expression normally peak during the period of synapse elimination, our findings identify axon-tethered NRG1 as a molecular determinant for SC-driven neuromuscular synaptic plasticity.
synapse elimination, neuromuscular junction, Schwann cell, neuregulin1, synaptic competition
1To whom correspondence may be addressed.
Author contributions: Y.i.L., Y.L., and W.J.T. designed research; Y.i.L., Y.L., M.M., and W.J.T. performed research; K.-A.N. and M.H.S. contributed new reagents/analytic tools; Y.i.L., I.S., and W.J.T. analyzed data; and Y.i.L., M.H.S., and W.J.T. wrote the paper.
논문정보
- Research article
- 2016년 01월 (BRIC 등록일 2016-01-18)
- 국외 연구진
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