DIFFERENTIAL MODULATION OF SERCA2 ISOFORMS BY CALRETICULIN

In Xenopus laevis oocytes, overexpression of calreticulin suppresses i nositol 1,4,5-trisphosphate-induced Ca2+ oscillations in a manner cons istent with inhibition of Ca2+ uptake into the endoplasmic reticulum. Here we report that the alternatively spliced isoforms of the sarcoend oplasmic reticulum Ca2+-ATPase (SERCA)2 gene display differential Ca2 wave properties and sensitivity to modulation by calreticulin. We dem onstrate by glucosidase inhibition and site-directed mutagenesis that a putative glycosylated residue (N1036) in SERCA2b is critical in dete rmining both the selective targeting of calreticulin to SERCA2b and is oform functional differences. Calreticulin belongs to a novel class of lectin ER chaperones that modulate immature protein folding. In addit ion to this role, we suggest that these chaperones dynamically modulat e the conformation of mature glycoproteins, thereby affecting their fu nction.