Degradation of exogenous membrane proteins implanted into the plasma membrane of cultured hepatoma cells.

The degradation of radiolabeled red cell band 3 and Sendai envelope proteins was studied after band 3 virosomes were fused with hepatoma cells as previously described (Hare, J E & Huston, M, Exp cell res 161 (1986) 317) [26]. 125I-band 3 (T1/2 = 13-14 h), Sendai HN (T1/2 = 37-40 h), and F (T1/2 = 21-23 h) envelope proteins were degraded by an apparent first-order process that was greater than 90% sensitive to 20 mM NH4Cl. 125I-Sendai envelope proteins were degraded at approximately similar rates when hepatoma cells were fused with intact virus, isolated viral membrane, or band 3 virosomes. There thus appears to be distinct heterogeneity among the degradation rates of implanted polypeptides dependent on structural aspects of each. To identify the subcellular site of membrane protein degradation, band 3 was labeled with membrane impermeant [14C]sucrose and implanted into hepatoma plasma membranes. After replating, trichloroacetic acid (TCA)-soluble label was found to accumulate in the lysosomal compartment of fractionated cells. The results identify the lysosome as the ultimate site of plasma membrane protein degradation, but suggest that plasma membrane proteins are selectively rather than non-selectively delivered to this compartment.