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.