RT Journal Article
SR Electronic
T1 Protein Kinase A Mediates Activity-Dependent Kv4.2 Channel Trafficking
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 7513
OP 7519
DO 10.1523/JNEUROSCI.1951-08.2008
VO 28
IS 30
A1 Hammond, Rebecca S.
A1 Lin, Lin
A1 Sidorov, Michael S.
A1 Wikenheiser, Andrew M.
A1 Hoffman, Dax A.
YR 2008
UL http://www.jneurosci.org/content/28/30/7513.abstract
AB The A-type potassium channel subunit Kv4.2 influences hippocampal function through regulation of dendritic excitability, and changes in Kv4.2 surface expression alter synaptic plasticity. Recent data from our laboratory demonstrate that EGFP (enhanced green fluorescent protein)-tagged Kv4.2 channels located in dendritic spines are internalized in an activity-dependent manner after synaptic stimulation and during chemically induced long-term potentiation. However, the molecular trigger for Kv4.2 internalization remains unknown. Here we examined the role of protein kinase A (PKA) in Kv4.2 activity-dependent trafficking. In hippocampal neurons, PKA activation with forskolin or 8-Br-cAMP induced Kv4.2 internalization from dendritic spines, whereas PKA inhibition with H89 prevented AMPA-induced internalization. Furthermore, introduction of a point mutation at the C-terminal PKA phosphorylation site of Kv4.2 (S552A) prevented the AMPA-induced internalization of Kv4.2. Together, these data demonstrate that Kv4.2 activity-dependent internalization requires PKA phosphorylation of Kv4.2 at serine 522.