A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1
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A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1. / Kilisch, Markus; Lytovchenko, Olga; Arakel, Eric C; Bertinetti, Daniela; Schwappach, Blanche.
In: J CELL SCI, Vol. 129, No. 4, 15.02.2016, p. 831-42.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - A dual phosphorylation switch controls 14-3-3-dependent cell surface expression of TASK-1
AU - Kilisch, Markus
AU - Lytovchenko, Olga
AU - Arakel, Eric C
AU - Bertinetti, Daniela
AU - Schwappach, Blanche
N1 - © 2016. Published by The Company of Biologists Ltd.
PY - 2016/2/15
Y1 - 2016/2/15
N2 - 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.
AB - 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.
KW - 14-3-3 Proteins/chemistry
KW - Amino Acid Sequence
KW - Animals
KW - COS Cells
KW - Cell Membrane
KW - Chlorocebus aethiops
KW - Coat Protein Complex I/metabolism
KW - Humans
KW - Nerve Tissue Proteins/chemistry
KW - Phosphorylation
KW - Potassium Channels, Tandem Pore Domain/chemistry
KW - Protein Binding
KW - Protein Interaction Domains and Motifs
KW - Protein Processing, Post-Translational
KW - Protein Transport
U2 - 10.1242/jcs.180182
DO - 10.1242/jcs.180182
M3 - SCORING: Journal article
C2 - 26743085
VL - 129
SP - 831
EP - 842
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - 4
ER -
