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Originally published In Press as doi:10.1074/jbc.M106116200 on January 14, 2002
J. Biol. Chem., Vol. 277, Issue 12, 10614-10625, March 22, 2002
Regulation of Neuromuscular Synapse Development by Glial Cell
Line-derived Neurotrophic Factor and Neurturin*
Chang-Yu
Wang §¶,
Feng
Yang ¶,
Xiang-Ping
He ,
Hyun-Soo
Je §,
Jian-Zheng
Zhou ,
Kary
Eckermann ,
David
Kawamura ,
Linyin
Feng ,
Liya
Shen**, and
Bai
Lu 
From the Unit on Synapse Development and Plasticity,
NICHD, National Institutes of Health, Bethesda, Maryland 20892, the
§ Genetics Graduate Program, George Washington University,
Washington, D.C. 20052, the ** Laboratory of Cellular
Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health,
Bethesda, Maryland 20892, and the Institute of Neuroscience,
Chinese Academy of Sciences, Shanghai, China 200031
Glial cell line-derived neurotrophic factor
(GDNF) is known for its potent effect on neuronal survival, but its
role in the development and function of synapses is not well studied.
Using Xenopus nerve-muscle co-cultures, we show that GDNF
and its family member neurturin (NRTN) facilitate the development of
the neuromuscular junction (NMJ). Long-term application of GDNF
significantly increased the total length of neurites in the
motoneurons. GDNF also caused an increase in the number and the size of
synaptic vesicle clustering, as demonstrated by synaptobrevin-GFP
fluorescent imaging, and FM dye staining. Electrophysiological
experiments revealed two effects of GDNF on synaptic transmission at
NMJ. First, GDNF markedly increased the frequency of spontaneous
transmission and decreased the variability of evoked transmission,
suggesting an enhancement of transmitter secretion. Second, GDNF
elicited a small increase in the quantal size, without affecting the
average rise and decay times of synaptic currents. Imaging analysis
showed that the size of acetylcholine receptor clusters at
synapses increased in muscle cells overexpressing GDNF. Neurturin had
very similar effects as GDNF. These results suggest that GDNF and NRTN
are new neuromodulators that regulate the development of the
neuromuscular synapse through both pre- and postsynaptic mechanisms.
*
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
¶
These authors contributed equally to the results of this work.

To whom correspondence should be addressed: Unit on Synapse
Development and Plasticity, NICHD, National Institutes of Health, Bldg.
49, Rm. 6A-80, 49 Convent Dr., MSC4480, Bethesda, MD 20892-4480. Tel.: 301-435-2970; Fax: 301-496-1777; E-mail: lub@codon.nih.gov.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.

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Copyright © 2002 by the American Society for Biochemistry and Molecular Biology.
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