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 pathway. Since CAML is widely expressed in mammalian tissues, it may be an important regulator of Ca²⁺ store function. In the present study, we investigated the consequence of CAML overexpression on Ca²⁺ signaling using rapid confocal imaging of Fluo3-loaded NIH3T3 fibroblasts. Control and CAML-expressing cells gave concentration-dependent responses to the Ca²⁺ mobilizing agonist ATP. CAML expression reduced the sensitivity of the cells so that higher concentrations of ATP were needed to achieve global Ca²⁺ waves. The amplitudes of Ca²⁺ waves were significantly reduced in CAML expressing cells, consistent with earlier suggestions that CAML causes depletion of internal Ca²⁺ stores. With low ATP concentrations, only local Ca²⁺ release events were observed. CAML did not affect the characteristics of these local Ca²⁺ signals, suggesting that it does not directly affect Ca²⁺ release channels. (C) 2000 Academic Press.