title: KRAS-induced actin-interacting protein regulates inositol 1,4,5-trisphosphate-receptor-mediated calcium release.
abstract: KRAS-induced actin-interacting protein (KRAP) was originally characterized as a filamentous- actin-interacting protein. We have recently found that KRAP is an associated molecule with inositol 1,4,5-trisphosphate (IP(3)) receptor (IP(3)R) and is responsible for the proper subcellular localization of IP(3)R. Since it remains unknown whether KRAP regulates the IP(3)R-mediated Ca(2+) signaling, we herein examined the effects of KRAP on the IP(3)R-mediated Ca(2+) release by Ca(2+) imagings in the cultured HEK293 or MCF7 cells. Reduction of KRAP protein by KRAP-specific siRNA diminishes ATP-induced Ca(2+) release and the ATP-induced Ca(2+) release is completely quenched by the pretreatment with the IP(3)R inhibitor but not with the ryanodine receptor inhibitor, indicating that KRAP regulates IP(3)R-mediated Ca(2+) release. To further reveal mechanistic insights into the regulation of IP(3)R-mediated Ca(2+) release by KRAP, we examined the effects of the KRAP-knockdown on the releasable Ca(2+) content of intracellular Ca(2+) stores. Consequently, reduction of KRAP does not affect the amount of ionophore- or Ca(2+)-ATPase inhibitor-induced Ca(2+) release in the HEK293 cells, indicating that releasable Ca(2+) content of intracellular Ca(2+) stores is not altered by KRAP. Thus, KRAP is involved in the proper regulation of IP(3)R-mediated Ca(2+) release.
authors: Department of Cell Biology, Faculty of Medicine, and Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan.
authors: Takahiro
authors: T
authors: Fujimoto
authors: Takashi
authors: T
authors: Machida
authors: Toshiyuki
authors: T
authors: Tsunoda
authors: Keiko
authors: K
authors: Doi
authors: Takeharu
authors: T
authors: Ota
authors: Masahide
authors: M
authors: Kuroki
authors: Senji
authors: S
authors: Shirasawa
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D045744:Cell Line, Tumor; D057809:HEK293 Cells; D006801:Humans; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C482653:ITPRID2 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; C557477:KRAP protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D002118:Calcium