Milenkovic, Vladimir M. and Krejcova, Sarka and Reichhart, Nadine and Wagner, Andrea and Strauss, Olaf (2011) Interaction of Bestrophin-1 and Ca2+ Channel beta-Subunits: Identification of New Binding Domains on the Bestrophin-1 C-Terminus. PLOS ONE, 6 (4): e19364. ISSN 1932-6203,
Full text not available from this repository. (Request a copy)Abstract
Bestrophin-1 modulates currents through voltage-dependent L-type Ca2+ channels by physically interacting with the beta-subunits of Ca2+ channels. The main function of beta-subunits is to regulate the number of pore-forming Ca-V-subunits in the cell membrane and modulate Ca2+ channel currents. To understand the influence of full-length bestrophin-1 on beta-subunit function, we studied binding and localization of bestrophin-1 and Ca2+ channel subunits, together with modulation of Ca(V)1.3 Ca2+ channels currents. In heterologeous expression, bestrophin-1 showed co-immunoprecipitation with either, beta 3-, or beta 4-subunits. We identified a new highly conserved cluster of proline-rich motifs on the bestrophin-1 C-terminus between amino acid position 468 and 486, which enables possible binding to SH3-domains of beta-subunits. A bestrophin-1 that lacks these proline-rich motifs (Delta CT-PxxP bestrophin-1) showed reduced efficiency to co-immunoprecipitate with beta 3 and beta 4-subunits. In the presence of Delta CT-PxxP bestrophin-1, beta 4-subunits and Ca(V)1.3 subunits partly lost membrane localization. Currents from Ca(V)1.3 subunits were modified in the presence of beta 4-subunit and wild-type bestrophin-1: accelerated time-dependent activation and reduced current density. With Delta CTPxxP bestrophin-1, currents showed the same time-dependent activation as with wild-type bestrophin-1, but the current density was further reduced due to decreased number of Ca2+ channels proteins in the cell membrane. In summary, we described new proline-rich motifs on bestrophin-1 C-terminus, which help to maintain the ability of beta-subunits to regulate surface expression of pore-forming Ca-V Ca2+-channel subunits.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VITELLIFORM MACULAR DYSTROPHY; RETINAL-PIGMENT EPITHELIUM; GATED CALCIUM-CHANNELS; BEST-DISEASE; LIGHT PEAK; MUTATIONS; GENE; VMD2; ACTIVATION; MEMBRANE; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Augenheilkunde |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 22 Jun 2020 09:12 |
| Last Modified: | 22 Jun 2020 09:12 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20927 |
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