Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation (J Biol Chem, 2008, 283:28198-28215)

報告日期: 2009/06/02
報告時間: 15:10/16:00
報告學生: 陳怡婷
講評老師: 沈孟儒
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/980602-1.pdf 

Role of sigma-1 receptor C-terminal segment in inositol 1,4,5-trisphosphate receptor activation: constitutive enhancement of calcium signaling in MCF-7 tumor cells.

J Biol Chem. 2008 Oct 17;283(42):28198-215.

Speaker: 陳怡婷 

Commentator: 沈孟儒 老師

Date: 02/06/2009/ pm15:10-16:00

Place: Room 602

 

Abstract

        Sigma receptor expressed not only in brain, but also in peripheral tissue and tumor cell lines. The sigma-1 receptor has been found to form a complex with ankyrin B and IP3R type 3 (IP3R-3) in neuroblastoma. In order to explore functions of sigma-1 receptors and the relationship of receptor structure to function, MCF-7 breast tumor cells express little or no sigma-1R and were used to investigate the effect of overexpression of sigma-1R and the function of its N- and C-terminal segments. The authors constructed cell lines11 and 41(transfected MCF-7 cells to express intact sigma-1R), and line K3 (expressed N-fragment of sigma-1R), and line sg101 (expressed C-fragment of sigma-1R). Comparing with normal [3H](+)-pentazocine binding activity for sigma-1R clone, N- and C- segment of sigma-1R clones exhibited low affinity and no binding activity, respectively. All constructed cell lines enhance bradykinin (BDK)-induced calcium release, because of a decrease in BDK ED50 values. Vasopressin- and ATP-induced calcium release also showed the same pattern in all cell lines. The sigma-1R antagonist BD1063 played an inverse agonist in cell lines 11, 41 and K3, but not in sg101, because of C-segment was insensitive to ligand regulation. Immunoprecipitation by anti-IP3R-3 antibody, ankyrin B 220 less associated in sigma-1R or C-segment clones, compared with parental MCF-7 or N-segment clone. Previous study showed ankyrin B inhibited IP3 receptor via binding with IP3R c-terminal. Immunoprecipitation by anti-ankyrin B, sigma-1R more associated in sigma-1R or C-segment clones,  but not in N-segment. The findings suggest that the sigma-1 receptor binds to ankyrin B 220 via its C-segment and causes BDK-stimulated calcium release via IP3R-3, dissociating it from ankyrin B 220 inhibition.

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