Calcium-modulating cyclophilin ligand desensitizes hormone-evoked calcium release

The Ca2+-modulating cyclophilin ligand (CAML) protein causes stimulation of transcription factors via activation of a store-operated Ca2+ entry pathwa y. Since CAML is widely expressed in mammalian tissues, it may be an import ant regulator of Ca2+ store function. In the present study, we investigated the consequence of CAML overexpression on Ca2+ signaling using rapid confo cal imaging of Fluo3-loaded NIH3T3 fibroblasts. Control and CAML-expressing cells gave concentration-dependent responses to the Ca2+ mobilizing agonis t ATP. CAML expression reduced the sensitivity of the cells so that higher concentrations of ATP were needed to achieve global Ca2+ waves. The amplitu des of Ca2+ waves were significantly reduced in CAML expressing cells, cons istent with earlier suggestions that CAML causes depletion of internal Ca2 stores. With low ATP concentrations, only local Ca2+ release events were o bserved. CAML did not affect the characteristics of these local Ca2+ signal s, suggesting that it does not directly affect Ca2+ release channels. (C) 2 000 Academic Press.