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© The Rockefeller University Press, 0021-9525/1998//963 $5.00
The Journal of Cell Biology, Volume 142, Number 4, , 1998 963-973


Articles

Differential Modulation of SERCA2 Isoforms by Calreticulin



Linu M. John*, James D. Lechleiter{ddagger}, and Patricia Camacho§

* Department of Biomedical Engineering, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908; {ddagger} Department of Molecular Medicine, Institute of Biotechnology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78245; and § Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284

In Xenopus laevis oocytes, overexpression of calreticulin suppresses inositol 1,4,5-trisphosphate-induced Ca2+ oscillations in a manner consistent with inhibition of Ca2+ uptake into the endoplasmic reticulum. Here we report that the alternatively spliced isoforms of the sarcoendoplasmic reticulum Ca2+-ATPase (SERCA)2 gene display differential Ca2+ wave properties and sensitivity to modulation by calreticulin. We demonstrate by glucosidase inhibition and site-directed mutagenesis that a putative glycosylated residue (N1036) in SERCA2b is critical in determining both the selective targeting of calreticulin to SERCA2b and isoform functional differences. Calreticulin belongs to a novel class of lectin ER chaperones that modulate immature protein folding. In addition to this role, we suggest that these chaperones dynamically modulate the conformation of mature glycoproteins, thereby affecting their function.

Key Words: calreticulin • Ca2+-ATPases • Ca2+ waves • confocal imaging • ER lectin chaperones



Abbreviations used in this paper: DNJ, deoxynojirimicin; GFP, green fluorescent protein; IP3R, Inositol 1,4,5-trisphosphate receptor; SERCA, Sarco endoplasmic reticulum calcium ATPase.

Address all correspondence to Patricia Camacho, Ph.D., Department of Physiology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78284-7756. Tel.: (210) 567-6558. Fax: (210) 567-4410. E-mail: camacho{at}uthscsa.edu



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