Regulation of AChR Clustering by Dishevelled Interacting with MuSK and PAK1
| Autor: | Anthony Wynshaw-Boris, Mingyao Liu, Qiang Wang, Bai Lu, Wen Cheng Xiong, Zhijun Luo, Xi He, Jian Z Zhou, Jianbo Wang, Zhen G Luo, Lin Mei |
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| Rok vydání: | 2002 |
| Předmět: |
Male
animal structures Macromolecular Substances Neuroscience(all) Dishevelled Proteins Neuromuscular Junction Protein Serine-Threonine Kinases Xenopus Proteins Biology Neuromuscular junction Xenopus laevis Anterior Horn Cells Neurotransmitter receptor Postsynaptic potential medicine Animals Humans Receptors Cholinergic Agrin Muscle Skeletal Cells Cultured Adaptor Proteins Signal Transducing Acetylcholine receptor chemistry.chemical_classification General Neuroscience Gene Expression Regulation Developmental Receptor Protein-Tyrosine Kinases Cell Differentiation Phosphoproteins Coculture Techniques Protein Structure Tertiary Dishevelled Nicotinic acetylcholine receptor medicine.anatomical_structure p21-Activated Kinases nervous system chemistry Oocytes Female Signal transduction Neuroscience Signal Transduction |
| Zdroj: | Neuron. 35(3):489-505 |
| ISSN: | 0896-6273 |
| DOI: | 10.1016/s0896-6273(02)00783-3 |
| Popis: | An important aspect of synapse development is the clustering of neurotransmitter receptors in the postsynaptic membrane. Although MuSK is required for acetylcholine receptor (AChR) clustering at the neuromuscular junction (NMJ), the underlying molecular mechanisms remain unclear. We report here that in muscle cells, MuSK interacts with Dishevelled (Dvl), a signaling molecule important for planar cell polarity. Disruption of the MuSK-Dvl interaction inhibits Agrin- and neuron-induced AChR clustering. Expression of dominant-negative Dvl1 in postsynaptic muscle cells reduces the amplitude of spontaneous synaptic currents at the NMJ. Moreover, Dvl1 interacts with downstream kinase PAK1. Agrin activates PAK, and this activation requires Dvl. Inhibition of PAK1 activity attenuates AChR clustering. These results demonstrate important roles of Dvl and PAK in Agrin/MuSK-induced AChR clustering and reveal a novel function of Dvl in synapse development. |
| Databáze: | OpenAIRE |
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