Article - 
Limited access to UNIGEOther version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196195/pdf/0102073.pdf
Highlights
More informations
Scientific Article
unige:7440 
 |
Functional specialization of calreticulin domains |
|
| Authors | 
| |
| Published in | The Journal of Cell Biology. 2001, vol. 154, no. 5, p. 961-972 | |
| Abstract | Calreticulin is a Ca2+-binding chaperone in the endoplasmic reticulum (ER), and calreticulin gene knockout is embryonic lethal. Here, we used calreticulin-deficient mouse embryonic fibroblasts to examine the function of calreticulin 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 inhibited Ca2+ release in response to bradykinin, yet they release Ca2+ upon direct activation with the inositol 1,4,5-trisphosphate (InsP3). These cells fail to produce a measurable level of InsP3 upon stimulation with bradykinin, 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 bradykinin receptor, which affects its ability to initiate InsP3-dependent Ca2+ release in calreticulin-deficient cells. We concluded that the C domain of calreticulin plays a role in Ca2+ storage and that the N domain may participate in its chaperone functions. | |
| Keywords | Animals — Bradykinin/pharmacology — Calcium/ metabolism — Calcium Channels/genetics/metabolism — Calcium-Binding Proteins/genetics/ metabolism — Calcium-Transporting ATPases/metabolism — Calreticulin — Cell Line — Endoplasmic Reticulum/ metabolism — Enzyme Inhibitors/pharmacology — Fibroblasts/drug effects/physiology — Flow Cytometry — Homeostasis — Immunoblotting — Inositol 1,4,5-Trisphosphate Receptors — Mice — Mice, Knockout — Microscopy, Fluorescence — Molecular Chaperones/genetics/metabolism — Protein Isoforms/genetics/metabolism — Protein Structure, Tertiary — Receptors, Bradykinin/metabolism — Receptors, Cytoplasmic and Nuclear/genetics/metabolism — Ribonucleoproteins/genetics/ metabolism — Sarcoplasmic Reticulum Calcium-Transporting ATPases — Thapsigargin/pharmacology — Transfection | |
| Identifiers | PMID: 11524434 | |
| Full text |
Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2196195/pdf/0102073.pdf |
|
| Structures | ||
| Citation (ISO format) | NAKAMURA, K. et al. Functional specialization of calreticulin domains. In: The Journal of Cell Biology, 2001, vol. 154, n° 5, p. 961-972. https://archive-ouverte.unige.ch/unige:7440 |
185 hits 
0 download 
Contact an author
Update