Neuronal Ca2+ sensor 1, the mammalian homologue of frequenin, is expressed in chromaffin and PC12 cells and regulates neurosecretion from dense-core granules.
Neuronal Ca2+ sensor 1 (NCS-1) is the mammalian homologue of the Ca2+-binding protein frequenin previously implicated in regulation of neurotransmission in Drosophila (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) Neuron 11, 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.
The Physiological Laboratory, University of Liverpool, Crown Street, Liverpool L69 3BX, United Kingdom.
B W
BW
McFerran
M E
ME
Graham
R D
RD
Burgoyne
D000313:Adrenal Medulla / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000378:metabolism*; D017931:DNA Primers; D051597:Hippocalcin; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D051596:Neurocalcin; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides / Q000378:metabolism*; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D044169:Receptors, Calcium-Sensing
D002135:Calcium-Binding Proteins; D017931:DNA Primers; D009419:Nerve Tissue Proteins; D051596:Neurocalcin; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D044169:Receptors, Calcium-Sensing; C496690:Vsnl1 protein, rat; C101464:frequenin calcium sensor proteins; D051597:Hippocalcin