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  • Title: Neuronal Ca2+ sensor-1/frequenin functions in an autocrine pathway regulating Ca2+ channels in bovine adrenal chromaffin cells.
    Author: Weiss JL, Archer DA, Burgoyne RD.
    Journal: J Biol Chem; 2000 Dec 22; 275(51):40082-7. PubMed ID: 11006299.
    Abstract:
    NCS-1/frequenin belongs to a family of EF-hand-containing Ca(2+) sensors expressed mainly in neurons. Overexpression of NCS-1/frequenin has been shown to stimulate neurotransmitter release but little else is known of its cellular roles. We have constructed an EF-hand mutant, NCS-1(E120Q), as a likely dominant inhibitor of cellular NCS-1 function. Recombinant NCS-1(E120Q) showed an impaired Ca(2+)-dependent conformational change but could still bind to cellular proteins. Transient expression of this mutant, but not NCS-1, in bovine adrenal chromaffin cells increased non-L-type Ca(2+) channel currents. Cells expressing NCS-1(E120Q) no longer responded effectively to the removal of autocrine purinergic/opioid inhibition of Ca(2+) currents but still showed voltage-dependent facilitation. These data are consistent with the existence of both voltage-dependent and voltage-independent pathways for Ca(2+) channel inhibition in chromaffin cells. Our results suggest a novel function for NCS-1 specific for the voltage-independent autocrine pathway that negatively regulates non-L-type Ca(2+) channels in chromaffin cells.
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