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| Content Provider | PubMed Central |
|---|---|
| Author | Nakamura, Kimitoshi Anna, Zuppini Arnaudeau, Serge Lynch, Jeffery Ahsan, Irfan Krause, Ryoko Papp, Sylvia De Smedt, Humbert Parys, Jan B. Werner, Müller-esterl Lew, Daniel P. Krause, Karl-heinz Nicolas, Demaurex Opas, Michal Michalak, Marek |
| 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. |
| Related Links | http://dx.doi.org/10.1083/jcb.200102073 |
| Starting Page | 961 |
| File Format | |
| ISSN | 15408140 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 5 |
| Volume Number | 154 |
| Language | English |
| Publisher | The Rockefeller University Press |
| Publisher Date | 2001-09-03 |
| Access Restriction | Open |
| Rights Holder | The Rockefeller University Press |
| Subject Keyword | Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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