Tuning the electrical properties of the heart by differential trafficking of KATP ion channel complexes
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Tuning the electrical properties of the heart by differential trafficking of KATP ion channel complexes. / Arakel, Eric C; Brandenburg, Sören; Uchida, Keita; Zhang, Haixia; Lin, Yu-Wen; Kohl, Tobias; Schrul, Bianca; Sulkin, Matthew S; Efimov, Igor R; Nichols, Colin G; Lehnart, Stephan E; Schwappach, Blanche.
In: J CELL SCI, Vol. 127, No. Pt 9, 01.05.2014, p. 2106-19.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Tuning the electrical properties of the heart by differential trafficking of KATP ion channel complexes
AU - Arakel, Eric C
AU - Brandenburg, Sören
AU - Uchida, Keita
AU - Zhang, Haixia
AU - Lin, Yu-Wen
AU - Kohl, Tobias
AU - Schrul, Bianca
AU - Sulkin, Matthew S
AU - Efimov, Igor R
AU - Nichols, Colin G
AU - Lehnart, Stephan E
AU - Schwappach, Blanche
PY - 2014/5/1
Y1 - 2014/5/1
N2 - The copy number of membrane proteins at the cell surface is tightly regulated. Many ion channels and receptors present retrieval motifs to COPI vesicle coats and are retained in the early secretory pathway. In some cases, the interaction with COPI is prevented by binding to 14-3-3 proteins. However, the functional significance of this antagonism between COPI and 14-3-3 in terminally differentiated cells is unknown. Here, we show that ATP-sensitive K(+) (KATP) channels, which are composed of Kir6.2 and SUR1 subunits, are stalled in the Golgi complex of ventricular, but not atrial, cardiomyocytes. Upon sustained β-adrenergic stimulation, which leads to activation of protein kinase A (PKA), SUR1-containing channels reach the plasma membrane of ventricular cells. We show that PKA-dependent phosphorylation of the C-terminus of Kir6.2 decreases binding to COPI and, thereby, silences the arginine-based retrieval signal. Thus, activation of the sympathetic nervous system releases this population of KATP channels from storage in the Golgi and, hence, might facilitate the adaptive response to metabolic challenges.
AB - The copy number of membrane proteins at the cell surface is tightly regulated. Many ion channels and receptors present retrieval motifs to COPI vesicle coats and are retained in the early secretory pathway. In some cases, the interaction with COPI is prevented by binding to 14-3-3 proteins. However, the functional significance of this antagonism between COPI and 14-3-3 in terminally differentiated cells is unknown. Here, we show that ATP-sensitive K(+) (KATP) channels, which are composed of Kir6.2 and SUR1 subunits, are stalled in the Golgi complex of ventricular, but not atrial, cardiomyocytes. Upon sustained β-adrenergic stimulation, which leads to activation of protein kinase A (PKA), SUR1-containing channels reach the plasma membrane of ventricular cells. We show that PKA-dependent phosphorylation of the C-terminus of Kir6.2 decreases binding to COPI and, thereby, silences the arginine-based retrieval signal. Thus, activation of the sympathetic nervous system releases this population of KATP channels from storage in the Golgi and, hence, might facilitate the adaptive response to metabolic challenges.
KW - 14-3-3 Proteins/metabolism
KW - Animals
KW - Blotting, Western
KW - Cells, Cultured
KW - Chromatography, Affinity
KW - Electrophysiology
KW - Fluorescent Antibody Technique, Indirect
KW - Immunoprecipitation
KW - KATP Channels/metabolism
KW - Male
KW - Mice
KW - Mice, Knockout
KW - Potassium Channels, Inwardly Rectifying/metabolism
KW - Protein Transport/physiology
KW - Sulfonylurea Receptors/metabolism
U2 - 10.1242/jcs.141440
DO - 10.1242/jcs.141440
M3 - SCORING: Journal article
C2 - 24569881
VL - 127
SP - 2106
EP - 2119
JO - J CELL SCI
JF - J CELL SCI
SN - 0021-9533
IS - Pt 9
ER -