title: SAP97 directs the localization of Kv4.2 to spines in hippocampal neurons: regulation by CaMKII.
abstract: The pore-forming alpha-subunit Kv4.2 is a key constituent of the A-type channel and critically involved in the regulation of dendritic excitability and plasticity. Here we show that Kv4.2 is enriched in the postsynaptic density (PSD) fraction and specifically interacts with synapse-associated protein 97 (SAP97). This interaction requires an intact C terminus of Kv4.2 and occurs via the PDZ domains of SAP97. Pharmacologically induced translocation of SAP97 to spines also drives Kv4.2 to the PSD, whereas SAP97 lentivirally based RNA interference reduces Kv4.2 in the PSD. In addition, calcium/calmodulin-dependent protein kinase II (CaMKII)-dependent SAP97 phosphorylation regulates the subcellular localization of Kv4.2. These results show that SAP97-CaMKII pathway plays an important role for the trafficking of Kv4.2 to dendrites and spines.
authors.affiliation: Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Gardoni
authors.affiliation: Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
authors.forename: Daniela
authors.initials: D
authors.lastname: Mauceri
authors.affiliation: Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Marcello
authors.affiliation: Cellular and Molecular Pharmacology Section, Institute of Neuroscience, Consiglio Nazionale Ricerche, and Department of Pharmacology, University of Milan, 20129 Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala
authors.affiliation: Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
authors.forename: Monica
authors.initials: M
authors.lastname: Di Luca
authors.affiliation: Center for Learning and Memory, University of Texas, Austin, Texas 78712. Electronic address: andreasj@alleninstitute.org.
authors.forename: Andreas
authors.initials: A
authors.lastname: Jeromin
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D002522:Chlorocebus aethiops; D003712:Dendrites / Q000235:genetics / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D016086:Lentivirus; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology; D010766:Phosphorylation; D017434:Protein Structure, Tertiary / Q000502:physiology; D021381:Protein Transport / Q000502:physiology; D034622:RNA Interference; D051381:Rats; D051672:Shal Potassium Channels / Q000235:genetics / Q000378:metabolism*; D013569:Synapses / Q000235:genetics / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C501119:Dlg1 protein, rat; D008565:Membrane Proteins; D051672:Shal Potassium Channels; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases