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.