A novel 145 kd brain cytosolic protein reconstitutes Ca super(2+)-regulated secretion in permeable neuroendocrine cells

The regulated secretory pathway is activated by elevated cytoplasmic Ca super(2+); however, the components mediating Ca super(2+) regulation have not been identified. In semi-intact neuroendocrine cells, Ca super(2+)-activated secretion is ATP- and cytosol protein-dependent. We have identified a novel brain protein, p145, as a cytosolic factor that reconstitutes Ca super(2+)-activated secretion in two neuroendocrine cell types. The protein is a dimer of 145 kd subunits, exhibits Ca super(2+)-dependent interaction with a hydrophobic matrix, and binds phospholipid vesicles, suggesting a membrane-associated function. A p145-specific antibody inhibits the reconstitution of Ca super(2+)-activated secretion by cytosol, indicating an essential role for p145. The restricted expression of p145 in tissues exhibiting a regulated secretory pathway suggests a key role for this protein in the transduction of Ca super(2+) signals into vectorial membrane fusion events.