SEL1L and HRD1 are involved in the degradation of unassembled secretory Ig-mu chains

Abstract

When expressed in the absence of light chains, secretory Ig-micro chains (micro(s)) undergo endoplasmic reticulum associated degradation (ERAD). This process involves the recognition of terminally misfolded or unassembled molecules, their retro-translocation across the ER membrane and ubiquitination for degradation by cytosolic proteasomes. The molecular components of the ERAD pathway and their coordination remain largely unknown. Here we employed co-immunoprecipitation, silencing or over-expression assays to show that SEL1L and HRD1 are involved in the degradation of unassembled Ig-micro(s), but have minor effects on another substrate, TCR-alpha. SEL1L and HRD1 localize in the early secretory apparatus and are induced by ER stress and during B cell differentiation, concomitantly with the onset of massive IgM secretion. These findings reveal a role for SEL1L and HRD1 in IgM quality control.