title: Calcium-modulating cyclophilin ligand desensitizes hormone-evoked calcium release.
abstract: The Ca(2+)-modulating cyclophilin ligand (CAML) protein causes stimulation of transcription factors via activation of a store-operated Ca(2+) entry pathway. Since CAML is widely expressed in mammalian tissues, it may be an important regulator of Ca(2+) store function. In the present study, we investigated the consequence of CAML overexpression on Ca(2+) signaling using rapid confocal imaging of Fluo3-loaded NIH3T3 fibroblasts. Control and CAML-expressing cells gave concentration-dependent responses to the Ca(2+) mobilizing agonist ATP. CAML expression reduced the sensitivity of the cells so that higher concentrations of ATP were needed to achieve global Ca(2+) waves. The amplitudes of Ca(2+) waves were significantly reduced in CAML expressing cells, consistent with earlier suggestions that CAML causes depletion of internal Ca(2+) stores. With low ATP concentrations, only local Ca(2+) release events were observed. CAML did not affect the characteristics of these local Ca(2+) signals, suggesting that it does not directly affect Ca(2+) release channels.
authors.affiliation: Laboratory of Molecular Signalling, Babraham Institute, Babraham, Cambridge, CB2 4AT, United Kingdom.
authors.forename: S C
authors.initials: SC
authors.lastname: Tovey
authors.forename: M D
authors.initials: MD
authors.lastname: Bootman
authors.forename: P
authors.initials: P
authors.lastname: Lipp
authors.forename: M J
authors.initials: MJ
authors.lastname: Berridge
authors.forename: R J
authors.initials: RJ
authors.lastname: Bram
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing; D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D001692:Biological Transport; D002118:Calcium / Q000502:physiology*; D002352:Carrier Proteins / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D051379:Mice; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C490314:Caml protein, mouse; D002352:Carrier Proteins; D000255:Adenosine Triphosphate; D002118:Calcium