%0 Journal Article
%T NMDA receptor activation stimulates transcription-independent rapid wnt5a protein synthesis via the MAPK signaling pathway
%A Yichen Li
%A Bei Li
%A Xianzi Wan
%A Wei Zhang
%A Ling Zhong
%A Shao-Jun Tang
%J Molecular Brain
%D 2012
%I BioMed Central
%R 10.1186/1756-6606-5-1
%X Wnts are secreted glycoproteins that regulate cell morphologies and behaviors by stimulating complicate intracellular signaling cascades. Previous work has established that Wnt signaling controls many oncogenic and developmental processes [1,2]. More recent studies have revealed that Wnt signaling is critically involved in key processes of the formation and plasticity of the nervous system, including neurogenesis [3], axon guidance [4], dendritic development [5], synaptic differentiation [6] and plasticity [7,8]. Abnormalities of Wnt signaling are implicated in major brain disorders such as Alzheimer's disease [9-11], Parkinson's disease [12,13], schizophrenia [14,15], and drug abuse [16]. Wnt5a is member of the Wnt protein family and plays important roles in outgrowth, guidance and branching of axons [17,18]; genesis of dopaminergic neurons [19]; and formation and plasticity of both excitatory and inhibitory synapses [20-22]. Wnt5a administration was reported to improve specific pathological processes of Alzheimer's [11] and Parkinson's diseases in animal models [12].Wnt proteins bind to receptors to activate the Wnt/¦Â-catenin canonical pathway and ¦Â-catenin-independent non-canonical pathways, which include the planar cell polarity (PCP) pathway and the Wnt/calcium (Ca2+) pathway [2,23-26]. In the canonical pathway, Wnts (such as Wnt3a) inhibit glycogen synthase kinase 3¦Â (GSK-3¦Â) and consequently stabilize ¦Â-catenin to regulate transcription [1]. Wnt5a is a prototypic Wnt ligand that activates the non-canonical pathways [27,28]. The activation of the PCP pathway stimulates Rho GTPases and c-Jun N-terminal kinase (JNK) to regulate cell morphogenesis and movement [29], whereas the activation of the Wnt/Ca2+ pathway causes Ca2+ to activate protein kinase C (PKC) and calcium/calmodulin dependent protein kinase II (CaMKII) [30]. In neurons, Wnt secretion is intimately governed by synaptic activity, especially the activation of NMDA receptors (NMDAR) [7].In contrast to
%K activity-regulated protein synthesis
%K Wnt protein
%K mTOR signaling
%K MAPK signaling
%K NMDA receptors
%U http://www.molecularbrain.com/content/5/1/1