Densin-180 Controls the Trafficking and Signaling of L-Type Voltage-Gated Cav1.2 Ca2+Channels at Excitatory Synapses

• DOI: 10.1523/jneurosci.2583-16.2017
• Publication Date: 2017-04-01T01:00:18Z
• Authors: Shiyi Wang; Ruslan I. Stanika; Xiaohan Wang; Jussara Hagen; Mary B. Kennedy; Gerald J. Obermair; Roger J. Colbran; Amy Lee
• Keywords: Cerebral Cortex; Male; Mice, Knockout; Neurons; 0301 basic medicine; 571; Calcium Channels, L-Type; Sialoglycoproteins; Excitatory Postsynaptic Potentials; Mice, Inbred C57BL; Mice; Protein Transport; 03 medical and health sciences; Synapses; Animals; Calcium Signaling; Ion Channel Gating; Signal Transduction

Voltage-gated Cav1.2 and Cav1.3 (L-type) Ca2+ channels regulate neuronal excitability, synaptic plasticity, learning memory. Densin-180 (densin) is an excitatory protein that promotes Ca2+-dependent facilitation of voltage-gated in transfected cells. Mice lacking densin (densin KO) exhibit defects spatial memory, increased anxiety-related behaviors-phenotypes more closely match those mice than Cav1.3. Therefore, we investigated the functional impact on Cav1.2. We report essential regulator neurons, but has distinct modulatory effects compared with its regulation Densin binds to N-terminal domain Cav1.2, not Cav1.3, increases currents cells neurons. In cells, accelerates forward trafficking without affecting their endocytosis. Consistent a role for increasing number postsynaptic channels, overexpression clustering dendrites hippocampal neurons culture. Compared wild-type mice, cell surface levels brain, as well current density signaling nucleus, are reduced from KO mice. conclude Cav1 ensures efficient at synapses.SIGNIFICANCE STATEMENT The localization Cav crucial determinants excitability transmission. densin-180 highly enriched synapses brain enhances L-type This interaction coupling activity-dependent gene transcription. Our results reveal mechanism may contribute roles regulating cognition mood.