TY - JOUR
T1 - Golgi export of the Kir2.1 channel is driven by a trafficking signal located within its tertiary structure
AU - Ma, Donghui
AU - Taneja, Tarvinder Kaur
AU - Hagen, Brian M.
AU - Kim, Bo Young
AU - Ortega, Bernardo
AU - Lederer, W. Jonathan
AU - Welling, Paul A.
N1 - Funding Information:
This project was supported by funds from the NIH (P01 HL70709, R01 DK54231, R01 DK 63049, and T32-HL-072751) and the American Heart Association (0855321E). We thank Drs. Ora Weisz and S. Kornberg for reagents, Dr. Terry Rogers for support and advice, and Dr. William R. Randall for help with adenovirus production.
PY - 2011/6/24
Y1 - 2011/6/24
N2 - Mechanisms that are responsible for sorting newly synthesized proteins for traffic to the cell surface from the Golgi are poorly understood. Here, we show that the potassium channel Kir2.1, mutations in which are associated with Andersen-Tawil syndrome, is selected as cargo into Golgi export carriers in an unusual signal-dependent manner. Unlike conventional trafficking signals, which are typically comprised of short linear peptide sequences, Golgi exit of Kir2.1 is dictated by residues that are embedded within the confluence of two separate domains. This signal patch forms a recognition site for interaction with the AP1 adaptor complex, thereby marking Kir2.1 for incorporation into clathrin-coated vesicles at the trans-Golgi. The identification of a trafficking signal in the tertiary structure of Kir2.1 reveals a quality control step that couples protein conformation to Golgi export and provides molecular insight into how mutations in Kir2.1 arrest the channels at the Golgi.
AB - Mechanisms that are responsible for sorting newly synthesized proteins for traffic to the cell surface from the Golgi are poorly understood. Here, we show that the potassium channel Kir2.1, mutations in which are associated with Andersen-Tawil syndrome, is selected as cargo into Golgi export carriers in an unusual signal-dependent manner. Unlike conventional trafficking signals, which are typically comprised of short linear peptide sequences, Golgi exit of Kir2.1 is dictated by residues that are embedded within the confluence of two separate domains. This signal patch forms a recognition site for interaction with the AP1 adaptor complex, thereby marking Kir2.1 for incorporation into clathrin-coated vesicles at the trans-Golgi. The identification of a trafficking signal in the tertiary structure of Kir2.1 reveals a quality control step that couples protein conformation to Golgi export and provides molecular insight into how mutations in Kir2.1 arrest the channels at the Golgi.
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U2 - 10.1016/j.cell.2011.06.007
DO - 10.1016/j.cell.2011.06.007
M3 - Article
C2 - 21703452
AN - SCOPUS:79959668938
SN - 0092-8674
VL - 145
SP - 1102
EP - 1115
JO - Cell
JF - Cell
IS - 7
ER -