p11, an annexin II subunit, an auxiliary protein associated with the background K+ channel, TASK-1.
TASK-1 belongs to the 2P domain K+ channel family and is the prototype of background K+ channels that set the resting membrane potential and tune action potential duration. Its activity is highly regulated by hormones and neurotransmitters. Although numerous auxiliary proteins have been described to modify biophysical, pharmacological and expression properties of different voltage- and Ca2+-sensitive K+ channels, none of them is known to modulate 2P domain K+ channel activity. We show here that p11 interacts specifically with the TASK-1 K+ channel. p11 is a subunit of annexin II, a cytoplasmic protein thought to bind and organize specialized membrane cytoskeleton compartments. This association with p11 requires the integrity of the last three C-terminal amino acids, Ser-Ser-Val, in TASK-1. Using series of C-terminal TASK-1 deletion mutants and several TASK-1-GFP chimeras, we demonstrate that association with p11 is essential for trafficking of TASK-1 to the plasma membrane. p11 association with the TASK-1 channel masks an endoplasmic reticulum retention signal identified as Lys-Arg-Arg that precedes the Ser-Ser-Val sequence.
Institut de Pharmacologie Moléculaire et Cellulaire, CNRS-UMR 6097, 660 route des Lucioles, Sophia Antipolis, 06560 Valbonne, France.
Christophe
C
Girard
Norbert
N
Tinel
Cécile
C
Terrenoire
Georges
G
Romey
Michel
M
Lazdunski
Marc
M
Borsotto
D000595:Amino Acid Sequence; D000818:Animals; D017306:Annexin A2 / Q000737:chemistry; D001667:Binding, Competitive; D019556:COS Cells; D002135:Calcium-Binding Proteins / Q000737:chemistry* / Q000378:metabolism* / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D002522:Chlorocebus aethiops; D015638:Cytochalasin D / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D015221:Potassium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D024683:Potassium Channels, Tandem Pore Domain; D025941:Protein Interaction Mapping; D017434:Protein Structure, Tertiary; D021122:Protein Subunits; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D009418:S100 Proteins; D017384:Sequence Deletion; D020798:Two-Hybrid System Techniques; D014633:Valine / Q000737:chemistry; D000099248:S100 Calcium Binding Protein A10
D017306:Annexin A2; D002135:Calcium-Binding Proteins; D015638:Cytochalasin D; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D009418:S100 Proteins; D014633:Valine; D000099248:S100 Calcium Binding Protein A10; C420132:potassium channel subfamily K member 3