title: Transducing neuronal activity into dendritic spine morphology: new roles for p38 MAP kinase and N-cadherin.
abstract: Synaptic plasticity depends on the generation, modification and disconnection of synapses. An excitatory synapse is connected to a specialized dendritic compartment called a spine, which undergoes activity-induced remodeling. Here, we discuss a signaling pathway that transduces neuronal activity into the remodeling of spine through p38 mitogen-activated protein kinase (MAPK) and N-cadherin. Dendritic spines change their morphology and density in response to neuronal activity. In the early phase, posttranslational modifications of synaptic molecules regulate spine morphology, whereas activity-induced gene products reduce spine density in the late phase. One of the targets of these mechanisms is N-cadherin. An activity-induced protocadherin, arcadlin, stimulates thousand and one 2beta (TAO2beta) kinase, which in turn activates p38 MAPK through MAPK kinase 3 (MEK3), resulting in the endocytosis of N-cadherin and the decrease in spine number. This pathway also underlies the mechanism of the spine decrease in neuronal disorders, such as Alzheimer's disease and epilepsy. Development of new p38 MAPK inhibitors brings a ray of hope with respect to the development of more effective therapies for these patients.
authors.affiliation: Department of Neuropharmacology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Sugiura
authors.forename: Hidekazu
authors.initials: H
authors.lastname: Tanaka
authors.forename: Shin
authors.initials: S
authors.lastname: Yasuda
authors.forename: Takako
authors.initials: T
authors.lastname: Takemiya
authors.forename: Kanato
authors.initials: K
authors.lastname: Yamagata
mesh_terms: D000818:Animals; D015820:Cadherins / Q000378:metabolism*; D049229:Dendritic Spines / Q000502:physiology* / Q000648:ultrastructure; D008954:Models, Biological; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D015820:Cadherins; D048051:p38 Mitogen-Activated Protein Kinases