eprintid: 10083027 rev_number: 20 eprint_status: archive userid: 608 dir: disk0/10/08/30/27 datestamp: 2019-10-10 11:54:02 lastmod: 2021-10-04 01:08:56 status_changed: 2019-10-10 11:54:02 type: article metadata_visibility: show creators_name: Meyer, JO creators_name: Dahimene, S creators_name: Page, KM creators_name: Ferron, L creators_name: Kadurin, I creators_name: Ellaway, JIJ creators_name: Zhao, P creators_name: Patel, T creators_name: Rothwell, SW creators_name: Lin, P creators_name: Pratt, WS creators_name: Dolphin, AC title: Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking ispublished: pub divisions: UCL divisions: B02 divisions: C08 divisions: D09 divisions: G02 keywords: N-type, P/Q-type, calcium channel, calcium currents, divalent cation, permeation, selectivity filter, trafficking, α(2)δ subunit, β subunit note: This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ abstract: Voltage-gated calcium channels are exquisitely Ca2+ selective, conferred primarily by four conserved pore-loop glutamate residues contributing to the selectivity filter. There has been little previous work directly measuring whether the trafficking of calcium channels requires their ability to bind Ca2+ in the selectivity filter or to conduct Ca2+. Here, we examine trafficking of neuronal CaV2.1 and 2.2 channels with mutations in their selectivity filter and find reduced trafficking to the cell surface in cell lines. Furthermore, in hippocampal neurons, there is reduced trafficking to the somatic plasma membrane, into neurites, and to presynaptic terminals. However, the CaV2.2 selectivity filter mutants are still influenced by auxiliary α2δ subunits and, albeit to a reduced extent, by β subunits, indicating the channels are not grossly misfolded. Our results indicate that Ca2+ binding in the pore of CaV2 channels may promote their correct trafficking, in combination with auxiliary subunits. Furthermore, physiological studies utilizing selectivity filter mutant CaV channels should be interpreted with caution. date: 2019-10-01 date_type: published official_url: https://doi.org/10.1016/j.celrep.2019.08.079 oa_status: green full_text_type: pub language: eng primo: open primo_central: open_green article_type_text: Journal Article verified: verified_manual elements_id: 1700706 doi: 10.1016/j.celrep.2019.08.079 pii: S2211-1247(19)31134-9 lyricists_name: Dolphin, Annette lyricists_name: Kadurin, Ivan lyricists_name: Page, Karen lyricists_id: ADOLP91 lyricists_id: IKADU83 lyricists_id: KMPAG96 actors_name: Kayal, Celine actors_name: Flynn, Bernadette actors_id: CKAYA67 actors_id: BFFLY94 actors_role: owner actors_role: impersonator full_text_status: public publication: Cell Reports volume: 29 number: 1 pagerange: 22-33.e5 event_location: United States issn: 2211-1247 citation: Meyer, JO; Dahimene, S; Page, KM; Ferron, L; Kadurin, I; Ellaway, JIJ; Zhao, P; ... Dolphin, AC; + view all <#> Meyer, JO; Dahimene, S; Page, KM; Ferron, L; Kadurin, I; Ellaway, JIJ; Zhao, P; Patel, T; Rothwell, SW; Lin, P; Pratt, WS; Dolphin, AC; - view fewer <#> (2019) Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking. Cell Reports , 29 (1) 22-33.e5. 10.1016/j.celrep.2019.08.079 <https://doi.org/10.1016/j.celrep.2019.08.079>. Green open access document_url: https://discovery.ucl.ac.uk/id/eprint/10083027/1/1-s2.0-S2211124719311349-main.pdf