title: Axin Regulates Dendritic Spine Morphogenesis through Cdc42-Dependent Signaling.
abstract: During development, scaffold proteins serve as important platforms for orchestrating signaling complexes to transduce extracellular stimuli into intracellular responses that regulate dendritic spine morphology and function. Axin ("axis inhibitor") is a key scaffold protein in canonical Wnt signaling that interacts with specific synaptic proteins. However, the cellular functions of these protein-protein interactions in dendritic spine morphology and synaptic regulation are unclear. Here, we report that Axin protein is enriched in synaptic fractions, colocalizes with the postsynaptic marker PSD-95 in cultured hippocampal neurons, and interacts with a signaling protein Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) in synaptosomal fractions. Axin depletion by shRNA in cultured neurons or intact hippocampal CA1 regions significantly reduced dendritic spine density. Intriguingly, the defective dendritic spine morphogenesis in Axin-knockdown neurons could be restored by overexpression of the small Rho-GTPase Cdc42, whose activity is regulated by CaMKII. Moreover, pharmacological stabilization of Axin resulted in increased dendritic spine number and spontaneous neurotransmission, while Axin stabilization in hippocampal neurons reduced the elimination of dendritic spines. Taken together, our findings suggest that Axin promotes dendritic spine stabilization through Cdc42-dependent cytoskeletal reorganization.
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Guangdong Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Zhuoyi
authors.initials: Z
authors.lastname: Liang
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Erkang
authors.initials: E
authors.lastname: Fei
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Guangdong Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, China.
authors.forename: Yuewen
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Xiaopu
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Weiqun
authors.initials: W
authors.lastname: Fang
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China.
authors.forename: Wing-Yu
authors.initials: WY
authors.lastname: Fu
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Guangdong Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, China.
authors.forename: Amy K Y
authors.initials: AK
authors.lastname: Fu
authors.affiliation: Division of Life Science, State Key Laboratory of Molecular Neuroscience and Molecular Neuroscience Center, The Hong Kong University of Science and Technology, Clear Water Bay, Kowloon, Hong Kong, China; Guangdong Key Laboratory of Brain Science, Disease and Drug Development, HKUST Shenzhen Research Institute, Shenzhen, Guangdong, China.
authors.forename: Nancy Y
authors.initials: NY
authors.lastname: Ip
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000235:genetics / Q000502:physiology*; D056547:CA1 Region, Hippocampal / Q000166:cytology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000378:metabolism; D002467:Cell Nucleus / Q000737:chemistry; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D049229:Dendritic Spines / Q000648:ultrastructure*; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology; D051379:Mice; D009024:Morphogenesis; D055495:Neurogenesis; D057907:Post-Synaptic Density / Q000737:chemistry; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D013574:Synaptosomes / Q000378:metabolism; D020764:cdc42 GTP-Binding Protein / Q000502:physiology*
chemical_list: D060466:Axin Protein; C555452:Axin1 protein, mouse; C581598:Cdc42 protein, mouse; D006575:Heterocyclic Compounds, 3-Ring; D034741:RNA, Small Interfering; C544261:XAV939; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D020764:cdc42 GTP-Binding Protein