#beta#m, 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

摘要

#beta#m, a muscle-specific protein, is structurally closely related to the X,K-ATPase #beta# subunits, but its intrinsic function is not known. In this stud, we have expressed #beta#m 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 #beta#m is stably expressed in the endoplamic reticulum (ER) in its core glycosylated, partially trimmed form. Both full-length #beta#m, initiated at Met, and short #beta#m species, initiated at Met~(89), are detected in vitro translations as well as in Xenopus oocytes. #beta#m cannot associate with and stabilize Na,K-ATPase (NK), or gastric and nongastric H,K-ATPase (HK) #alpha# isoforms. #beta#m 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 #beta#m N-terminus are deleted, remains stably expressed in the ER and can associate with, but not stabilize X,K-ATPase #alpha# subuits. On the other hand, a chimera in which the ectodomain of #beta#m is replaced with that of #beta#1 NK associates efficiently with #alpha# NK isoforms and produces functional Na,K-pumps at the plasma membrane. In conclusion, our results indicate that #beta#m exhibits a cellular location and functional role clearly distinct from the typical X,K-ATPase #beta# subunits.