Functional specialization of calreticulin domains
| Autor: | Humbert De Smedt, Anna Zuppini, Serge Arnaudeau, Nicolas Demaurex, Ryoko Krause, Jan B. Parys, Jeffery Lynch, Daniel Pablo Lew, Marek Michalak, Michal Opas, Karl-Heinz Krause, Kimitoshi Nakamura, Sylvia Papp, Werner Müller-Esterl, Irfan Ahsan |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
Calcium/ metabolism
Receptors Cytoplasmic and Nuclear Receptors Bradykinin/metabolism Endoplasmic Reticulum chemistry.chemical_compound Calcium-Transporting ATPases/metabolism Mice 0302 clinical medicine Calcium-binding protein Homeostasis Inositol 1 4 5-Trisphosphate Receptors Protein Isoforms Enzyme Inhibitors calreticulin-deficient cells calcium homeostasis chaperone bradykinin receptor endoplasmic reticulum ddc:616 Enzyme Inhibitors/pharmacology Mice Knockout 0303 health sciences biology Voltage-dependent calcium channel Protein Isoforms/genetics/metabolism Flow Cytometry Cell biology Receptors Cytoplasmic and Nuclear/genetics/metabolism Ribonucleoproteins 030220 oncology & carcinogenesis Thapsigargin Fibroblasts/drug effects/physiology Calcium-Binding Proteins/genetics/ metabolism Ribonucleoproteins/genetics/ metabolism Immunoblotting Bradykinin Calcium-Transporting ATPases Transfection Article Cell Line Sarcoplasmic Reticulum Calcium-Transporting ATPases 03 medical and health sciences Molecular Chaperones/genetics/metabolism Animals Thapsigargin/pharmacology Bradykinin receptor 030304 developmental biology Calcium Channels/genetics/metabolism Endoplasmic reticulum Receptors Bradykinin Calcium-Binding Proteins Cell Biology Endoplasmic Reticulum/ metabolism Fibroblasts Protein Structure Tertiary chemistry Bradykinin/pharmacology Microscopy Fluorescence Chaperone (protein) biology.protein Calcium Calcium Channels Calreticulin Molecular Chaperones |
| Zdroj: | The Journal of Cell Biology The Journal of Cell Biology, Vol. 154, No 5 (2001) pp. 961-972 |
| ISSN: | 0021-9525 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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