ENHANCED ACETYLCHOLINE-RELEASE FROM CELLS THAT HAVE MORE 15-KDA PROTEOLIPID IN THEIR MEMBRANE, A CONSTITUENT V-ATPASE, AND MEDIATOPHORE

Mediatophore is a protein that translocates acetylcholine (ACh) on cal cium action. It is a homopolymer of a 15-kDa proteolipid that is also a constituent of the membrane sector of vacuolar H+ -adenosine trispho sphatase (V-ATPase; vacuolar proton pump). Experiments on neuroblastom a cell lines (N18TG-2) that are deficient for ACh release and on cells that are competent for release, such as the glioma C6BU-1 or the N18T G-2/ C6BU-1 fusion product NG108-15, show that there is a correlation between ACh release and the 15-kDa proteolipid content of the cell mem brane. In another cell line, L-M(TK-), it has been possible to up-regu late ACh release and the membrane proteolipid content after treating t he cells with dibutyryl-cyclic AMP or dexamethasone. As mediatophore t ranslocates ACh and as V-ATPase may help vesicular ACh storage, it was interesting to determine the respective role of the two proteins in t he observed correlation between release and proteolipid content. After blocking vesicular loading with vesamicol, we did not affect release from these cells, suggesting that the observed correlation may be attr ibuted to mediatophore. The acquisition of an ACh release mechanism wo uld then depend on the process that guides the proteolipid to the plas ma membrane of the cell.