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
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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