INVESTIGADORES
BOLLO Mariana Ines
congresos y reuniones científicas
Título:
Dephosphorylation of calnexin by calcineurin is modulated by immunophilins
Autor/es:
BOLLO M, PAREDES R, RODERICK L, LECHLEITER JD AND CAMACHO P
Lugar:
Oxford, Reino Unido
Reunión:
Congreso; GORDON RESEARCH CONFERENCES, Calcium Signaling Conference.; 2005
Resumen:
Dephosphorylation of Calnexin by Calcineurin is Modulated by Immunophilins Mariana Bollo1*, R. Madelaine Paredes2, H. Llewelyn Roderick1,3, James D. Lechleiter2 and Patricia Camacho1. 1Department of Physiology MSC 7756, University of Texas Health Science Center at San Antonio (UTHSCSA), 7703 Floyd Curl Drive, San Antonio, TX 78229-3900 2 Department of Cellular and Structural Biology, UTHSCSA. 3 Current address: University of Cambridge, Department of Pharmacology, Cambridge, CB2 1PD, U.K. *Poster presenter Ca2+ oscillations in Xenopus oocytes are mainly controlled by two opposing mechanisms: Ca2+ release from the inositol 1,4,5-triphosphate receptors channels (IP3Rs) and re-uptake into Ca2+ stores by the Ca2+ ATPases. Our group has demonstrated that under resting conditions calnexin (CLNX), a lectin chaperone located in the membrane of the endoplasmic reticulum (ER), is phosphorylated and interacts with the carboxy-terminal of the sarco endoplasmic reticulum calcium ATPases 2b (SERCA2b). This interaction partially inhibits pump activity when Ca2+ stores are full. However pump activity is still sufficient to counteract the Ca2+ leak, maintaining luminal Ca2+ homeostasis at an optimal level for protein folding. When IP3-stimulated IP3Rs release Ca2+ from the ER the Ca2+ dependent protein folding machinery is stressed. To minimize ER stress, Ca2+ release from the ER also results in dephosphorylation of CLNX, which leads to loss of pump inhibition, thereby rapidly restoring optimal Ca2+ levels. We will present date demonstrating that in Xenopus oocytes, Calcineurin (CN), a Ca2+/CaM dependent phosphatase, differentially regulates the release and uptake of Ca2+ into the ER. We will show that two different pathways under the control of immunophilins, FKBP12 and Cyclophylin A are involved in this regulation. This work is funded by NIH RO1 GM55372 to P.C.