The transport of the K+ channels TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to the cell surface is controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels. The current model proposes that phosphorylation-dependent binding of 14-3-3 sterically masks a COPI-binding motif. However, the direct effects of phosphorylation on COPI binding and on the binding parameters of 14-3-3 isoforms are still unknown. We find that phosphorylation of the trafficking control region prevents COPI binding even in the absence of 14-3-3, and we present a quantitative analysis of the binding of all human 14-3-3 isoforms to the trafficking control regions of TASK-1 and TASK-3. Surprisingly, the affinities of 14-3-3 proteins for TASK-1 are two orders of magnitude lower than for TASK-3. Furthermore, we find that phosphorylation of a second serine residue in the C-terminus of TASK-1 inhibits 14-3-3 binding. Thus, phosphorylation of the trafficking control region can stimulate or inhibit transport of TASK-1 to the cell surface depending on the target serine residue. Our findings indicate that control of TASK-1 trafficking by COPI, kinases, phosphatases and 14-3-3 proteins is highly dynamic.
Description
A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 | Journal of Cell Science
%0 Journal Article
%1 Kilischjcs.180182
%A Kilisch, M.
%A Lytovchenko, O.
%A Arakel, E. C.
%A Bertinetti, D.
%A Schwappach, B.
%D 2016
%I The Company of Biologists Ltd
%J Journal of Cell Science
%K herberg myown
%N 4
%P 831-842
%R 10.1242/jcs.180182
%T A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1
%U http://jcs.biologists.org/content/129/4/831
%V 129
%X The transport of the K+ channels TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to the cell surface is controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels. The current model proposes that phosphorylation-dependent binding of 14-3-3 sterically masks a COPI-binding motif. However, the direct effects of phosphorylation on COPI binding and on the binding parameters of 14-3-3 isoforms are still unknown. We find that phosphorylation of the trafficking control region prevents COPI binding even in the absence of 14-3-3, and we present a quantitative analysis of the binding of all human 14-3-3 isoforms to the trafficking control regions of TASK-1 and TASK-3. Surprisingly, the affinities of 14-3-3 proteins for TASK-1 are two orders of magnitude lower than for TASK-3. Furthermore, we find that phosphorylation of a second serine residue in the C-terminus of TASK-1 inhibits 14-3-3 binding. Thus, phosphorylation of the trafficking control region can stimulate or inhibit transport of TASK-1 to the cell surface depending on the target serine residue. Our findings indicate that control of TASK-1 trafficking by COPI, kinases, phosphatases and 14-3-3 proteins is highly dynamic.
@article{Kilischjcs.180182,
abstract = {The transport of the K+ channels TASK-1 and TASK-3 (also known as KCNK3 and KCNK9, respectively) to the cell surface is controlled by the binding of 14-3-3 proteins to a trafficking control region at the extreme C-terminus of the channels. The current model proposes that phosphorylation-dependent binding of 14-3-3 sterically masks a COPI-binding motif. However, the direct effects of phosphorylation on COPI binding and on the binding parameters of 14-3-3 isoforms are still unknown. We find that phosphorylation of the trafficking control region prevents COPI binding even in the absence of 14-3-3, and we present a quantitative analysis of the binding of all human 14-3-3 isoforms to the trafficking control regions of TASK-1 and TASK-3. Surprisingly, the affinities of 14-3-3 proteins for TASK-1 are two orders of magnitude lower than for TASK-3. Furthermore, we find that phosphorylation of a second serine residue in the C-terminus of TASK-1 inhibits 14-3-3 binding. Thus, phosphorylation of the trafficking control region can stimulate or inhibit transport of TASK-1 to the cell surface depending on the target serine residue. Our findings indicate that control of TASK-1 trafficking by COPI, kinases, phosphatases and 14-3-3 proteins is highly dynamic.},
added-at = {2016-01-08T20:52:00.000+0100},
author = {Kilisch, M. and Lytovchenko, O. and Arakel, E. C. and Bertinetti, D. and Schwappach, B.},
biburl = {https://www.bibsonomy.org/bibtex/28f42374a42e4ed286c69533b59674ae9/biochemie},
description = {A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1 | Journal of Cell Science},
doi = {10.1242/jcs.180182},
eprint = {http://jcs.biologists.org/content/129/4/831.full.pdf},
interhash = {b022f0e2b5ab0b0fa08cff3ad329d2bb},
intrahash = {8f42374a42e4ed286c69533b59674ae9},
issn = {0021-9533},
journal = {Journal of Cell Science},
keywords = {herberg myown},
number = 4,
pages = {831-842},
publisher = {The Company of Biologists Ltd},
timestamp = {2016-11-04T10:39:16.000+0100},
title = {A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1},
url = {http://jcs.biologists.org/content/129/4/831},
volume = 129,
year = 2016
}