SAP97 directs the localization of Kv4.2 to spines in hippocampal neurons: regulation by CaMKII.
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.
Gardoni
Fabrizio
F
Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Mauceri
Daniela
D
Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Marcello
Elena
E
Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Sala
Carlo
C
Cellular and Molecular Pharmacology Section, Institute of Neuroscience, Consiglio Nazionale Ricerche, and Department of Pharmacology, University of Milan, 20129 Milan, Italy.
Di Luca
Monica
M
Department of Pharmacological Sciences and Center of Excellence on Neurodegenerative Diseases, University of Milan, via Balzaretti 9, 20133 Milan, Italy.
Jeromin
Andreas
A
Center for Learning and Memory, University of Texas, Austin, Texas 78712. Electronic address: andreasj@alleninstitute.org.
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
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