A NOVEL 145-KD BRAIN CYTOSOLIC PROTEIN RECONSTITUTES CA2+-REGULATED SECRETION IN PERMEABLE NEUROENDOCRINE CELLS

The regulated secretory pathway is activated by elevated cytoplasmic Ca2+; however, the components mediating Ca2+ regulation have not been identified. In semi-intact neuroendocrine cells, Ca2+-activated secretion is ATP- and cytosol protein-dependent. We have identified a novel brain protein, p145, as a cytosolic factor that reconstitutes Ca2+-activated secretion in two neuroendocrine cell types. The protein is a dimer of 145 kd subunits, exhibits Ca2+-dependent interaction with a hydrophobic matrix, and binds phospholipid vesicles, suggesting a membrane-associated function. A p145-specific antibody inhibits the reconstitution of Ca2+-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 Ca2+ signals into vectorial membrane fusion events.