A novel 145 kd brain cytosolic protein reconstitutes Ca(2+)-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, Ca(2+)-activated secretion is ATP- and cytosol protein-dependent. We have identified a novel brain protein, p145, as a cytosolic factor that reconstitutes Ca(2+)-activated secretion in two neuroendocrine cell types. The protein is a dimer of 145 kd subunits, exhibits Ca(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(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 Ca2+ signals into vectorial membrane fusion events.
Walent
J H
JH
Department of Zoology, University of Wisconsin, Madison 53706.
Porter
B W
BW
Martin
T F
TF
D000818:Animals; D001923:Brain Chemistry; D002118:Calcium / Q000378:metabolism*; D002135:Calcium-Binding Proteins; D003600:Cytosol / Q000737:chemistry; D005089:Exocytosis; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000302:isolation & purification* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D016716:PC12 Cells / Q000187:drug effects*; D051381:Rats
C485812:Cadps protein, rat; D002135:Calcium-Binding Proteins; D009419:Nerve Tissue Proteins; D002118:Calcium; D009638:Norepinephrine