Neuronal Ca2+ Sensor 1, the Mammalian Homologue of Frequenin, Is Expressed in Chromaffin and PC12 Cells and Regulates Neurosecretion from Dense-core Granules

• Published in: The Journal of biological chemistry Vol. 273; no. 35; pp. 22768 - 22772
• Main Authors: McFerran, Brian W., Graham, Margaret E., Burgoyne, Robert D.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.08.1998; American Society for Biochemistry and Molecular Biology
• Subjects: Adrenal Medulla - cytology; Adrenal Medulla - metabolism; Animals; Base Sequence; Calcium-Binding Proteins - metabolism; Cattle; Cells, Cultured; Chromaffin Cells - metabolism; Cytoplasmic Granules - metabolism; DNA Primers; Hippocalcin; Nerve Tissue Proteins - metabolism; Neurocalcin; Neuronal Calcium-Sensor Proteins; Neuropeptides - metabolism; PC12 Cells; Rats; Rats, Wistar; Receptors, Calcium-Sensing
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.273.35.22768

Neuronal Ca2+ sensor 1 (NCS-1) is the mammalian homologue of the Ca2+-binding protein frequenin previously implicated in regulation of neurotransmission inDrosophila (Pongs, O., Lindemeier, J., Zhu, X. R., Theil, T., Endelkamp, D., Krah-Jentgens, I., Lambrecht, H.-G., Koch, K. W., Schwemer, J., Rivosecchi, R., Mallart, A., Galceran, J., Canal, I., Barbas, J. A., and Ferrus, A. (1993) Neuron11, 15–28). NCS-1 has been considered to be expressed only in neurons, but we show that NCS-1 expression can be detected in bovine adrenal chromaffin and PC12 cells, two widely studied model neuroendocrine cells. NCS-1 was present in both cytosolic and membrane fractions including purified chromaffin granules, and in immunofluorescence, its distribution overlapped with peripheral punctate staining seen with the synaptic-like microvesicle marker synaptophysin in PC12 cells. The possible functional role of NCS-1 in exocytosis of dense-core granules was tested using transient transfection 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 may have a regulatory but not direct role in neurosecretion.