Post-translational modification and evoked release of two large surface proteins of sympathetic neurons.

Two high molecular weight glycoproteins, exposed on the surface of sympathetic neurons, are modified after they have been translated, glycosylated, and inserted in the plasma membrane. B1 (apparent Mr = 230,000 by electrophoresis in sodium dodecyl sulfate) and B3 (Mr approximately 200,000) are each modified to give proteins of lower apparent molecular weight: B2 (Mr approximately 215,000) and B4 (Mr approximately 185,000). B1 and B3 are derived from two precursors, P1 (Mr approximately 210,000) and P3 (Mr approximately 185,000) which are nonsialylated, mannose-rich proteins not exposed on the cell surface. In unstimulated cells, B1 and B3 are converted to B2 and B4 with a half-life of 4 to 6 hr. In cells which have been treated chemically to evoke the release of neurotransmitter, the modification appears to be accelerated, and B2 and B4 are shed into the medium in soluble form (S2 and S4). This evoked release of protein is calcium dependent and is detected only in conditions which favor the rapid release of neurotransmitter. In the absence of exogenous calcium, however, transmitter release can be evoked without the accompanying release of protein. Thus the release of protein is not an essential step of transmitter release, but may follow it. B1, its precursor, and derivatives are immunologically related to the NILE (nerve growth factor-inducible, large external) glycoprotein of pheochromocytoma PC12 cells (McGuire, J. C., L. A. Greene, and A. V. Furano (1978) Cell 15: 357-365). B3 does not cross-react with B1 or NILE antigenically, but otherwise is synthesized, processed, and released in a similar manner.