Regulation of synaptic growth and maturation by a synapse-associated E3 ubiquitin ligase at the neuromuscular junction.
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.
Mesh Terms:
Animals, Carrier Proteins, Endocytosis, Mice, Mice, Transgenic, Muscle Fibers, Skeletal, Muscle, Skeletal, Neuromuscular Junction, Receptor Protein-Tyrosine Kinases, Synapses, Ubiquitin-Protein Ligases, Zinc Fingers
Animals, Carrier Proteins, Endocytosis, Mice, Mice, Transgenic, Muscle Fibers, Skeletal, Muscle, Skeletal, Neuromuscular Junction, Receptor Protein-Tyrosine Kinases, Synapses, Ubiquitin-Protein Ligases, Zinc Fingers
J. Cell Biol.
Date: Jun. 18, 2007
PubMed ID: 17576800
View in: Pubmed Google Scholar
Download Curated Data For This Publication
96525
Switch View:
- Interactions 3
- PTM Genes 1