Selective Golgi export of Kir2.1 controls the stoichiometry of functional Kir2.x channel heteromers.
Surface expression of ion channels and receptors often depends on intrinsic sequence motifs that control their intracellular transport along the secretory pathway. Although members of the Kir2.x subfamily share two such motifs - a diacidic ER export motif and a positively charged Golgi export motif - they strongly differ in their surface expression. Whereas Kir2.1 shows prominent plasma membrane localization, Kir2.4 channels accumulate within the Golgi complex. By constructing chimeras between Kir2.1 and Kir2.4 subunits, a stretch of 20 amino acids was identified in the Kir2.1 C-terminus that is both necessary and sufficient to promote anterograde transport of Kir channel subunits at the level of trafficking from the Golgi to the plasma membrane. The core element of the identified sequence bears a tyrosine-dependent YXXPhi consensus motif for adaptin binding, with the flanking residues determining its functional efficiency. As the signal is dominant in promoting surface transport of Kir2.1/Kir2.4 channel heteromers and is recognized by both the epithelial and neuronal intracellular sorting machinery, the preferential Golgi export of Kir2.1 will control the stoichiometry of Kir2.x heteromers expressed on the cell surface.
Hofherr
Alexis
A
Department of Physiology II, University of Freiburg, Hermann-Herder-Str. 7, 79104 Freiburg, Germany.
Fakler
Bernd
B
Klöcker
Nikolaj
N
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D004848:Epithelium / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D049452:Green Fluorescent Proteins / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D009893:Opossums; D011188:Potassium / Q000737:chemistry; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism* / Q000502:physiology; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D014162:Transfection; D014443:Tyrosine / Q000737:chemistry
C489461:Kir2.1 channel; C489465:Kir2.4 channel; D024661:Potassium Channels, Inwardly Rectifying; D011993:Recombinant Fusion Proteins; D049452:Green Fluorescent Proteins; D014443:Tyrosine; D011188:Potassium