Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1

Zhen G. Luo, Qiang Wang, Jian Z. Zhou, Jianbo Wang, Zhijun Luo, Mingyao Liu, Xi He, Anthony Wynshaw-Boris, Wen C. Xiong, Bai Lu, Lin Mei

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)489-505
Number of pages17
JournalNeuron
Volume35
Issue number3
DOIs
StatePublished - Aug 1 2002
Externally publishedYes

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Cholinergic Receptors
Agrin
Cluster Analysis
Neuromuscular Junction
Synapses
Muscle Cells
p21-Activated Kinases
Cell Polarity
Neurotransmitter Receptor
Neurons
Membranes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Luo, Z. G., Wang, Q., Zhou, J. Z., Wang, J., Luo, Z., Liu, M., ... Mei, L. (2002). Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. Neuron, 35(3), 489-505. https://doi.org/10.1016/S0896-6273(02)00783-3

Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. / Luo, Zhen G.; Wang, Qiang; Zhou, Jian Z.; Wang, Jianbo; Luo, Zhijun; Liu, Mingyao; He, Xi; Wynshaw-Boris, Anthony; Xiong, Wen C.; Lu, Bai; Mei, Lin.

In: Neuron, Vol. 35, No. 3, 01.08.2002, p. 489-505.

Research output: Contribution to journalArticle

Luo, ZG, Wang, Q, Zhou, JZ, Wang, J, Luo, Z, Liu, M, He, X, Wynshaw-Boris, A, Xiong, WC, Lu, B & Mei, L 2002, 'Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1', Neuron, vol. 35, no. 3, pp. 489-505. https://doi.org/10.1016/S0896-6273(02)00783-3
Luo, Zhen G. ; Wang, Qiang ; Zhou, Jian Z. ; Wang, Jianbo ; Luo, Zhijun ; Liu, Mingyao ; He, Xi ; Wynshaw-Boris, Anthony ; Xiong, Wen C. ; Lu, Bai ; Mei, Lin. / Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1. In: Neuron. 2002 ; Vol. 35, No. 3. pp. 489-505.
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