Sci. STKE, 1 August 2006
CALCIUM SIGNALING New Ligand for IP3 Receptors?
Ca2+-binding proteins (CaBPs), a family of neuronally expressed proteins, were identified as interacting partners for inositol 1,4,5-trisphosphate receptors (IP3Rs). Based on the requirement for two of their four EF hand domains in this interaction, White et al. investigated whether more widely abundant EF hand domain-containing proteins associated with the endoplasmic reticulum might also bind to IP3Rs. CIB1 (for calcium- and integrin-binding protein, also known as calmyrin or KIP) interacted with all three isoforms of IP3Rs in glutathione S-transferase (GST) pull-down experiments and endogenous IP3R3 and CIB1 coimmunoprecipitated from cultured cells. CIB1 binding to IP3R was stimulated by calcium in an in vitro assay. Single-channel analysis of IP3R1 expressed in Xenopus oocytes indicated that CIB1 activated the receptors in the absence of IP3, although it was not as effective as IP3 at activating the receptors. However, both CaBP and CIB1 acted as inhibitors of IP3R-mediated calcium release when overexpressed in cultured cells. To reconcile these results, the authors examined IP3R activity of Sf9 cell nuclei in response to IP3 or after preexposure to CIB1 and found that preexposure to CIB1 decreased the number of channels activated by IP3. Thus, CIB1 may initially stimulate IP3R but may ultimately render the channels refractory to further stimulation.
C. White, J. Yang, M. J. Monteiro, J. K. Foskett, CIB1, a ubiquitously expressed Ca2+-binding protein ligand of the InsP3 receptor Ca2+ release channel. J. Biol. Chem. 281, 20825-20833 (2006). [Abstract] [Full Text]
Citation: New Ligand for IP3 Receptors? Sci. STKE 2006, tw259 (2006).
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