{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:44:27Z","timestamp":1784072667882,"version":"3.55.0"},"reference-count":65,"publisher":"Society for Neuroscience","issue":"18","license":[{"start":{"date-parts":[[2017,11,3]],"date-time":"2017-11-03T00:00:00Z","timestamp":1509667200000},"content-version":"vor","delay-in-days":217,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J. Neurosci."],"published-print":{"date-parts":[[2017,5,3]]},"abstract":"<jats:p>Voltage-gated Ca<jats:sub>v<\/jats:sub>1.2 and Ca<jats:sub>v<\/jats:sub>1.3 (L-type) Ca<jats:sup>2+<\/jats:sup>channels regulate neuronal excitability, synaptic plasticity, and learning and memory. Densin-180 (densin) is an excitatory synaptic protein that promotes Ca<jats:sup>2+<\/jats:sup>-dependent facilitation of voltage-gated Ca<jats:sub>v<\/jats:sub>1.3 Ca<jats:sup>2+<\/jats:sup>channels in transfected cells. Mice lacking densin (densin KO) exhibit defects in synaptic plasticity, spatial memory, and increased anxiety-related behaviors\u2014phenotypes that more closely match those in mice lacking Ca<jats:sub>v<\/jats:sub>1.2 than Ca<jats:sub>v<\/jats:sub>1.3. Therefore, we investigated the functional impact of densin on Ca<jats:sub>v<\/jats:sub>1.2. We report that densin is an essential regulator of Ca<jats:sub>v<\/jats:sub>1.2 in neurons, but has distinct modulatory effects compared with its regulation of Ca<jats:sub>v<\/jats:sub>1.3. Densin binds to the N-terminal domain of Ca<jats:sub>v<\/jats:sub>1.2, but not that of Ca<jats:sub>v<\/jats:sub>1.3, and increases Ca<jats:sub>v<\/jats:sub>1.2 currents in transfected cells and in neurons. In transfected cells, densin accelerates the forward trafficking of Ca<jats:sub>v<\/jats:sub>1.2 channels without affecting their endocytosis. Consistent with a role for densin in increasing the number of postsynaptic Ca<jats:sub>v<\/jats:sub>1.2 channels, overexpression of densin increases the clustering of Ca<jats:sub>v<\/jats:sub>1.2 in dendrites of hippocampal neurons in culture. Compared with wild-type mice, the cell surface levels of Ca<jats:sub>v<\/jats:sub>1.2 in the brain, as well as Ca<jats:sub>v<\/jats:sub>1.2 current density and signaling to the nucleus, are reduced in neurons from densin KO mice. We conclude that densin is an essential regulator of neuronal Ca<jats:sub>v<\/jats:sub>1 channels and ensures efficient Ca<jats:sub>v<\/jats:sub>1.2 Ca<jats:sup>2+<\/jats:sup>signaling at excitatory synapses.<\/jats:p><jats:p><jats:bold>SIGNIFICANCE STATEMENT<\/jats:bold>The number and localization of voltage-gated Ca<jats:sub>v<\/jats:sub>Ca<jats:sup>2+<\/jats:sup>channels are crucial determinants of neuronal excitability and synaptic transmission. We report that the protein densin-180 is highly enriched at excitatory synapses in the brain and enhances the cell surface trafficking and postsynaptic localization of Ca<jats:sub>v<\/jats:sub>1.2 L-type Ca<jats:sup>2+<\/jats:sup>channels in neurons. This interaction promotes coupling of Ca<jats:sub>v<\/jats:sub>1.2 channels to activity-dependent gene transcription. Our results reveal a mechanism that may contribute to the roles of Ca<jats:sub>v<\/jats:sub>1.2 in regulating cognition and mood.<\/jats:p>","DOI":"10.1523\/jneurosci.2583-16.2017","type":"journal-article","created":{"date-parts":[[2017,4,1]],"date-time":"2017-04-01T01:00:18Z","timestamp":1491008418000},"page":"4679-4691","source":"Crossref","is-referenced-by-count":35,"title":["Densin-180 Controls the Trafficking and Signaling of L-Type Voltage-Gated Ca<sub>v<\/sub>1.2 Ca<sup>2+<\/sup>Channels at Excitatory Synapses"],"prefix":"10.1523","volume":"37","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3433-3025","authenticated-orcid":false,"given":"Shiyi","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruslan 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