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Regulating ankyrin dynamics: Roles of sigma-1 receptors

2001; National Academy of Sciences; Volume: 98; Issue: 2 Linguagem: Inglês

10.1073/pnas.98.2.491

1091-6490

Teruo Hayashi, Tsung‐Ping Su,

Neuropeptides and Animal Physiology

Ankyrin is a cytoskeletal adaptor protein that controls important cellular functions, including Ca 2+ efflux at inositol 1,4,5-trisphosphate receptors (IP 3 R) on the endoplasmic reticulum. The present study found that sigma-1 receptors (Sig-1R), unique endoplasmic reticulum proteins that bind certain steroids, neuroleptics, and psychotropic drugs, form a trimeric complex with ankyrin B and IP 3 R type 3 (IP 3 R-3) in NG-108 cells. The trimeric complex could be coimmunoprecipitated by antibodies against any of the three proteins. Sig-1R agonists such as pregnenolone sulfate and cocaine caused the dissociation of an ankyrin B isoform (ANK 220) from IP 3 R-3. This effect caused by Sig-1R agonists was blocked by a Sig-1R antagonist. The degree of dissociation of ANK 220 from IP 3 R-3 caused by Sig-1R ligands correlates excellently with the ligands' efficacies in potentiating the bradykinin-induced increase in cytosolic free Ca 2+ concentration. Immunocytohistochemistry showed that Sig-1R, ankyrin B, and IP 3 R-3 are colocalized in NG-108 cells in perinuclear areas and in regions of cell-to-cell communication. These results suggest that Sig-1R and associated ligands may play important roles in cells by controlling the function of cytoskeletal proteins and that the Sig-1R/ANK220/IP 3 R-3 complex regulating Ca 2+ signaling may represent a site of action for neurosteroids and cocaine.