title: Betam, a structural member of the X,K-ATPase beta subunit family, resides in the ER and does not associate with any known X,K-ATPase alpha subunit.
abstract: betam, a muscle-specific protein, is structurally closely related to the X,K-ATPase beta subunits, but its intrinsic function is not known. In this study, we have expressed betam in Xenopus oocytes and have investigated its biosynthesis and processing as well as its putative role as a chaperone of X,K-ATPase alpha subunits, as a regulator of sarcoplasmic reticulum Ca(2+)-ATPase (SERCA), or as a Ca(2+)-sensing protein. Our results show that betam is stably expressed in the endoplasmic reticulum (ER) in its core glycosylated, partially trimmed form. Both full-length betam, initiated at Met(1), and short betam species, initiated at Met(89), are detected in in vitro translations as well as in Xenopus oocytes. betam cannot associate with and stabilize Na,K-ATPase (NK), or gastric and nongastric H,K-ATPase (HK) alpha isoforms. betam neither assembles stably with SERCA nor is its trypsin sensitivity or electrophoretic mobility influenced by Ca(2+). A mutant, in which the distinctive Glu-rich regions in the betam N-terminus are deleted, remains stably expressed in the ER and can associate with, but not stabilize X,K-ATPase alpha subunits. On the other hand, a chimera in which the ectodomain of betam is replaced with that of beta1 NK associates efficiently with alpha NK isoforms and produces functional Na,K-pumps at the plasma membrane. In conclusion, our results indicate that betam exhibits a cellular location and functional role clearly distinct from the typical X,K-ATPase beta subunits.
authors.affiliation: Institute of Pharmacology and Toxicology, University of Lausanne, rue du Bugnon 27, CH-1005 Lausanne, Switzerland.
authors.forename: Gilles
authors.initials: G
authors.lastname: Crambert
authors.forename: Pascal
authors.initials: P
authors.lastname: Béguin
authors.forename: Nikolay B
authors.initials: NB
authors.lastname: Pestov
authors.forename: Nikolai N
authors.initials: NN
authors.lastname: Modyanov
authors.forename: Käthi
authors.initials: K
authors.lastname: Geering
mesh_terms: D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D020740:Chimerin Proteins / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006023:Glycoproteins / Q000378:metabolism; D006031:Glycosylation; D017506:H(+)-K(+)-Exchanging ATPase / Q000737:chemistry; D006801:Humans; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones / Q000378:metabolism; D018482:Muscle, Skeletal; D009865:Oocytes / Q000378:metabolism; D021122:Protein Subunits; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase / Q000737:chemistry; D013329:Structure-Activity Relationship; D013552:Swine; D014018:Tissue Distribution; D014982:Xenopus laevis
chemical_list: D020740:Chimerin Proteins; D006023:Glycoproteins; D008562:Membrane Glycoproteins; D018832:Molecular Chaperones; D021122:Protein Subunits; D000251:Adenosine Triphosphatases; C442834:betam protein, Sus scrofa; D017506:H(+)-K(+)-Exchanging ATPase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium