NEURONAL CA2-1, THE MAMMALIAN HOMOLOG OF FREQUENIN, IS EXPRESSED IN CHROMAFFIN AND PC12 CELLS AND REGULATES NEUROSECRETION FROM DENSE-CORE GRANULES( SENSOR)

Neuronal Ca2+ sensor 1 (NCS-1) is the mammalian homologue of the Ca2+- binding protein frequenin previously implicated in regulation of neuro transmission in Drosophila (Pongs, O., Lindemeier, J., Zhu, X. R., The il, T., Endelkamp, D., Krah-Jentgens, I., Lambrecht, H.-G., Koch, R. W ., Schwemer, J., Rivosecchi, R., Mallart, A., Galceran, J., Canal, I., Barbas, J. A., and Ferrus, A. (1993) Neuron 11, 15-28). NCS-1 has bee n considered to be expressed only in neurons, but we show that NCS-1 e xpression can be detected in bovine adrenal chromaffin and PC12 cells, two widely studied model neuroendocrine cells. NCS-1 was present in b oth cytosolic and membrane fractions including purified chromaffin gra nules, and in immunofluorescence, its distribution overlapped with per ipheral punctate staining seen with the synaptic-like microvesicle mar ker synaptophysin in PC12 cells. The possible functional role of NCS-1 in exocytosis of dense core granules was tested using transient trans fection in PC12 cells and assay of co-transfected growth hormone (GH) release. Overexpression of NCS-1 increased evoked GH release in intact cells in response to ATP. No effect of overexpression was seen on GH release because of Ca2+ in permeabilized cells suggesting that NCS-1 m ay have a regulatory but not direct role in neurosecretion.