Phospholemman (FXYD1) associates with Na,K-ATPase and regulates its transport properties.
A family of small, single-span membrane proteins (the FXYD family) has recently been defined based on their sequence and structural homology. Some members of this family have already been identified as tissue-specific regulators of Na,K-ATPase (NKA). In the present study, we demonstrate that phospholemman (PLM) (FXYD1), so far considered to be a heart- and muscle-specific channel or channel-regulating protein, associates specifically and stably with six different alpha-beta isozymes of NKA after coexpression in Xenopus oocytes, and with alpha1-beta, and less efficiently with alpha2-beta isozymes, in native cardiac and skeletal muscles. Stoichiometric association of PLM with NKA occurs posttranslationally either in the Golgi or the plasma membrane. Interaction of PLM with NKA induces a small decrease in the external K+ affinity of alpha1-beta1 and alpha2-beta1 isozymes and a nearly 2-fold decrease in the internal Na+ affinity. In conclusion, this study demonstrates that PLM is a tissue-specific regulator of NKA that may play an essential role in muscle contractility.
Crambert
Gilles
G
Institute of Pharmacology and Toxicology, University of Lausanne, Rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
Fuzesi
Maria
M
Garty
Haim
H
Karlish
Steven
S
Geering
Kathi
K
D000818:Animals; D001692:Biological Transport; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002417:Cattle; D003001:Cloning, Molecular; D004285:Dogs; D004721:Endoplasmic Reticulum / Q000201:enzymology; D005260:Female; D006321:Heart / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000502:physiology; D008564:Membrane Potentials; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D018482:Muscle, Skeletal / Q000502:physiology; D009865:Oocytes / Q000502:physiology; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D021122:Protein Subunits; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D012519:Sarcoplasmic Reticulum / Q000201:enzymology; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014982:Xenopus laevis
D008565:Membrane Proteins; D010750:Phosphoproteins; D021122:Protein Subunits; D011994:Recombinant Proteins; C069141:phospholemman; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase