Diverse trafficking patterns due to multiple traffic motifs in G protein-activated inwardly rectifying potassium channels from brain and heart.
G protein-activated inwardly rectifying potassium channels (Kir3, GIRK) provide an important mechanism for neurotransmitter regulation of membrane excitability. GIRK channels are tetramers containing various combinations of Kir3 subunits (Kir3.1--Kir3.4). We find that different combinations of Kir3 subunits exhibit a surprisingly complex spectrum of trafficking phenotypes. Kir3.2 and Kir3.4, but not Kir3.1, contain ER export signals that are important for plasma membrane expression of Kir3.1/Kir3.2 and Kir3.1/Kir3.4 heterotetramers, the GIRK channels found in the brain and the heart, respectively. Additional motifs in Kir3.2 and Kir3.4 control the trafficking between endosome and plasma membrane. In contrast, the Kir3.3 subunit potently inhibits plasma membrane expression by diverting the heterotetrameric channels to lysosomes. Such rich trafficking behaviors provide a mechanism for dynamic regulation of GIRK channel density in the plasma membrane.
Ma
Dzwokai
D
Howard Hughes Medical Institute, University of California, San Francisco 94143, USA.
Zerangue
Noa
N
Raab-Graham
Kimberly
K
Fried
Sharon R
SR
Jan
Yuh Nung
YN
Jan
Lily Yeh
LY
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism*; D019556:COS Cells; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D004594:Electrophysiology; D004705:Endocytosis / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000378:metabolism; D006321:Heart / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D018613:Microscopy, Confocal; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009865:Oocytes / Q000502:physiology; D024661:Potassium Channels, Inwardly Rectifying / Q000737:chemistry / Q000378:metabolism*; D021382:Protein Sorting Signals; D021122:Protein Subunits; D021381:Protein Transport / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016415:Sequence Alignment
D016895:Culture Media, Serum-Free; D005456:Fluorescent Dyes; D024661:Potassium Channels, Inwardly Rectifying; D021382:Protein Sorting Signals; D021122:Protein Subunits