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Differential Regulation of Endocytic Trafficking in Kir2.x Channels
Author(s) -
Mason Amanda King,
Welling Paul A
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1332-a
Subject(s) - endocytic cycle , clathrin , microbiology and biotechnology , internalization , signal transducing adaptor protein , potassium channel , endocytosis , clathrin adaptor proteins , chemistry , biology , signal transduction , cell , biophysics , biochemistry
The inwardly rectifying family of potassium (Kir)2.x channels underlie the strong inward rectifier potassium current and set the resting membrane potential and conductance in many excitable and non‐excitable cells. Differential expression and regulation of Kir2.X isoforms have been suggested to underscore cell‐specific regulation of membrane excitability, but the mechanisms are unclear. Here, we explore whether Kir2.1 and Kir2.3 are controlled by channel‐specific endocytic and post‐endocytic trafficking mechanisms. We found that interaction with clathrin adaptor proteins differently regulate the cell surface density of Kir2.1 and Kir2.3. A diisoleucine motif, unique to carboxy‐terminus of the Kir2.3 channel, interacts with the clathrin adaptor AP‐2, and siRNA‐mediated suppression of the AP‐2 alpha subunit attenuates rapid internalization of Kir 2.3. By contrast, internalization of Kir2.1 is coordinated by a separate AP‐2 “YXXΦ” trafficking signal, uniquely directing Kir2.1 to the lysosomal pathway. In summary, while both channels depend on interaction with clathrin adaptor proteins for trafficking, the interaction motifs and ultimate fates of the channels differ. Supported by NIDDK, AHA, and NIGMS.