NDLI: Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junction

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Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junction

Content Provider	Scilit
Author	Lu, Zhonghua Je, Hyunsoo Young, Paul Gross, Jimmy Lu, Bai Feng, Guoping
Copyright Year	2007
Description	The ubiquitin–proteasome pathway has been implicated in synaptic development and plasticity. However, mechanisms by which ubiquitination contributes to precise and dynamic control of synaptic development and plasticity are poorly understood. We have identified a PDZ domain containing RING finger 3 (PDZRN3) as a synapse-associated E3 ubiquitin ligase and have demonstrated that it regulates the surface expression of muscle-specific receptor tyrosine kinase (MuSK), the key organizer of postsynaptic development at the mammalian neuromuscular junction. PDZRN3 binds to MuSK and promotes its ubiquitination. Regulation of cell surface levels of MuSK by PDZRN3 requires the ubiquitin ligase domain and is mediated by accelerated endocytosis. Gain- and loss-of-function studies in cultured myotubes show that regulation of MuSK by PDZRN3 plays an important role in MuSK-mediated nicotinic acetylcholine receptor clustering. Furthermore, overexpression of PDZRN3 in skeletal muscle of transgenic mice perturbs the growth and maturation of the neuromuscular junction. These results identify a synapse-associated E3 ubiquitin ligase as an important regulator of MuSK signaling.
Related Links	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2064367/pdf http://jcb.rupress.org/content/177/6/1077.full.pdf
Ending Page	1089
Page Count	13
Starting Page	1077
DOI	10.1083/jcb.200610060
Journal	Journal of Cell Biology
Issue Number	6
Volume Number	177
Language	English
Publisher	Rockefeller University Press
Publisher Date	2007-06-18
Access Restriction	Open
Subject Keyword	Cell Biology Regulation Plasticity Function Neuromuscular Junction Ubiquitin Ligase Musk Pdzrn3 Journal: Journal of Cell Biology (Vol- 177, Issue- 6)
Content Type	Text

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