Cutting edge: Proteasome involvement in the degradation of unassembled Ig light chains

Several studies on disposal of nonsecreted Ig L chains have identified the endoplasmic reticulum as the site of degradation. Here, we examine degradat ion of a nonsecreted Ig L chain, T15L, and an experimentally endoplasmic re ticulum-retained secretion-competent L chain, D16L, in the absence of H cha ins. We demonstrate that 1) degradation is specifically impaired by the pro teasome-specific inhibitors carboxybenzyl-leucyl-leucyl-leucine vinyl sulfo ne (Z-L3VS) and lactacystin, 2) L chain degradation occurs early in the bio synthetic pathway, and 3) degradation does not require vesicular transport. Our findings indicate that previous assertions of L chain disposal within the endoplasmic reticulum must be modified. To our knowledge, we provide th e first direct evidence supporting a new paradigm for removal of nonsecrete d Ig L chains via dislocation to cytosolic proteasomes.