Functional specialization of calreticulin domains

Citation
K. Nakamura et al., Functional specialization of calreticulin domains, J CELL BIOL, 154(5), 2001, pp. 961-972
Citations number
36
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Cell & Developmental Biology
Journal title
JOURNAL OF CELL BIOLOGY
ISSN journal
0021-9525 → ACNP
Volume
154
Issue
5
Year of publication
2001
Pages
961 - 972
Database
ISI
SICI code
0021-9525(20010903)154:5<961:FSOCD>2.0.ZU;2-#
Abstract
Calreticulin is a Ca2+-binding chaperone in the endoplasmic reticulum (ER), and calreticulin gene knockout is embryonic lethal. Here, we used calretic ulin-deficient mouse embryonic fibroblasts to examine the function of calre ticulin as a regulator of Ca2+ homeostasis. In cells without calreticulin, the ER has a lower capacity for Ca2+ storage, although the free ER luminal Ca2+ concentration is unchanged. Calreticulin-deficient cells show inhibite d Ca2+ release in response to bradykinin, yet they release Ca2+ upon direct activation with the inositol 1,4,5-trisphosphate (InsP(3)). These cells fa il to produce a measurable level of InsP(3) upon stimulation with bradykini n, likely because the binding of bradykinin to its cell surface receptor is impaired. Bradykinin binding and bradykinin-induced Ca2+ release are both restored by expression of full-length calreticulin and the N + P domain of the protein. Expression of the P + C domain of calreticulin does not affect bradykinin-induced Ca2+ release but restores the ER Ca2+ storage capacity. Our results indicate that calreticulin may play a role in folding of the b radykinin receptor, which affects its ability to initiate InsP(3)-dependent Ca2+ release in calreticulin-deficient cells. We concluded that the C doma in of calreticulin plays a role in Ca2+ storage and that the N domain may p articipate in its chaperone functions.