@article{discovery10083027, 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/}, journal = {Cell Reports}, pages = {22--33.e5}, month = {October}, title = {Disruption of the Key Ca2+ Binding Site in the Selectivity Filter of Neuronal Voltage-Gated Calcium Channels Inhibits Channel Trafficking}, number = {1}, volume = {29}, year = {2019}, 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 {\ensuremath{\alpha}}2{\ensuremath{\delta}} subunits and, albeit to a reduced extent, by {\ensuremath{\beta}} 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.}, url = {https://doi.org/10.1016/j.celrep.2019.08.079}, author = {Meyer, JO and Dahimene, S and Page, KM and Ferron, L and Kadurin, I and Ellaway, JIJ and Zhao, P and Patel, T and Rothwell, SW and Lin, P and Pratt, WS and Dolphin, AC}, keywords = {N-type, P/Q-type, calcium channel, calcium currents, divalent cation, permeation, selectivity filter, trafficking, {\ensuremath{\alpha}}(2){\ensuremath{\delta}} subunit, {\ensuremath{\beta}} subunit}, issn = {2211-1247} }