Research article summary (published 30 Jul 2002):

Regulation of AChR clustering by Dishevelled interacting with MuSK and PAK1.

Full 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.

Author information

Author/s: Luo, Zhen G (ZG); Wang, Qiang (Q); Zhou, Jian Z (JZ); Wang, Jianbo (J); Luo, Zhijun (Z); Liu, Mingyao (M); He, Xi (X); Wynshaw-Boris, Anthony (A); Xiong, Wen C (WC); Lu, Bai (B); Mei, Lin (L);

Affiliation: Department of Neurobiology, Civitan International Research Center, University of Alabama at Birmingham, 1530 Third Avenue South, Birmingham, AL 35294, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Neuron (Neuron), published in United States. (Language: eng)

Reference: 2002-Aug; vol 35 (issue 3) : pp 489-505

Dates: Created 2002/08/07; Completed 2002/09/04; Revised 2007/11/15;

PMID: 12165471, status: MEDLINE (last retrieval date: 2/18/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Adaptor Proteins, Signal Transducing Agrin - genetics; metabolism Animals Anterior Horn Cells - cytology; embryology; metabolism Cell Differentiation - physiology Cells, Cultured Coculture Techniques Female Gene Expression Regulation, Developmental - physiology Humans Macromolecular Substances Male

Male Muscle, Skeletal - cytology; embryology; metabolism Neuromuscular Junction - cytology; embryology; metabolism Oocytes Phosphoproteins - genetics; metabolism Protein Structure, Tertiary - physiology Protein-Serine-Threonine Kinases - genetics; metabolism Receptor Protein-Tyrosine Kinases - genetics; metabolism Receptors, Cholinergic - genetics; metabolism Signal Transduction - physiology Xenopus laevis p21-Activated Kinases

Associated Chemicals: Adaptor Proteins, Signal Transducing (0) ; Agrin (0) ; Macromolecular Substances (0) ; Phosphoproteins (0) ; Receptors, Cholinergic (0) ; dishevelled proteins (0) ; Receptor Protein-Tyrosine Kinases (EC 2.7.1.112) ; MUSK protein, human (EC 2.7.10.1) ; PAK1 protein, human (EC 2.7.11.1) ; Protein-Serine-Threonine Kinases (EC 2.7.11.1) ; p21-Activated Kinases (EC 2.7.11.1)

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