The role of Wnt/beta-catenin signaling in postsynaptic differentiation.
Synapses are basic units that mediate the communication between neurons and their target cells. The formation of synapse is regulated by secreted factors, receptors, adhesion molecules and intracellular signaling molecules. The interplay between positive and negative factors determines synapse assembling, remodeling and elimination, resulting in the formation of precise synaptic connections. However, compared to the abundant identified positive factors, negative factors are largely unknown. We have recently shown that Wnt3a acts as a negative factor that inhibits postsynaptic differentiation at the neuromuscular junction (NMJ), the synapse formed between motor neurons and skeletal muscle fibers. The clustering of acetylcholine receptor (AChR) guarantees efficient and accurate neurotransmission and is a hallmark for postsynaptic differentiation at the NMJ. We found that treatment with Wnt3a or upregulation of beta-catenin inhibited the formation of AChR clusters. Furthermore, we investigated the underlying mechanism and found that Wnt/beta-catenin signaling negatively regulated AChR clustering by downregulating the expression of Rapsyn, an AChR-associated protein required for formation and stabilization of AChR clusters.
Wang
Jia
J
Institute of Neuroscience and Key Laboratory of Neurobiology; Chinese Academy of Sciences; Shanghai P.R. China.
Luo
Zhen-Ge
ZG
Cell. 2000 Mar 3;100(5):525-35
10721990
Nat Neurosci. 2008 Mar;11(3):262-8
18278041
J Biol Chem. 2008 Aug 1;283(31):21668-75
18541538
Cell. 2004 Jul 23;118(2):257-70
15260994
Neuron. 2007 Jul 19;55(2):247-60
17640526
Nat Neurosci. 2001 Apr;4(4):374-81
11276227
J Cell Biol. 2000 Sep 18;150(6):1399-410
10995444
Cell. 2001 May 18;105(4):533-45
11371349
Nat Neurosci. 2003 Oct;6(10):1017-8
14502292
Nat Neurosci. 2001 Nov;4(11):1093-101
11593233
Neuron. 2006 Jun 15;50(6):897-909
16772171
Neuron. 2002 Aug 1;35(3):489-505
12165471
Annu Rev Neurosci. 2005;28:251-74
16022596
J Biol Chem. 1993 Jan 5;268(1):719-25
7678010
Nat Rev Neurosci. 2001 Nov;2(11):791-805
11715056
Cell. 2007 Aug 24;130(4):704-16
17719547
Proc Natl Acad Sci U S A. 1999 Feb 2;96(3):1112-7
9927702
Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):11088-93
16043708
Nat Cell Biol. 2003 Mar;5(3):179-82
12646868
Annu Rev Neurosci. 1999;22:389-442
10202544
Annu Rev Cell Dev Biol. 1997;13:119-46
9442870
J Biol Chem. 2004 Jul 23;279(30):31622-8
15155732
J Biol Chem. 2006 Apr 28;281(17):11910-6
16501258
Neuron. 2003 Nov 13;40(4):703-17
14622576
Neuron. 2005 May 19;46(4):569-79
15944126
Neuron. 2002 Sep 12;35(6):1043-56
12354395
J Neurosci. 2007 Apr 11;27(15):3968-73
17428970