Cattaneo Monica, Otsu Mieko, Fagioli Claudio, Martino Simone, Lotti Lavinia Vittoria, Sitia Roberto, Biunno Ida
Institute for Biomedical Technologies, National Research Council, Segrate, Milan, Italy.
J Cell Physiol. 2008 Jun;215(3):794-802. doi: 10.1002/jcp.21364.
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.
当在没有轻链的情况下表达时，分泌型Ig-μ链（μ(s)）会经历内质网相关降解（ERAD）。这个过程涉及对终末错误折叠或未组装分子的识别、它们跨内质网膜的逆向转运以及通过胞质蛋白酶体进行泛素化降解。ERAD途径的分子成分及其协调作用在很大程度上仍然未知。在这里，我们采用了共免疫沉淀、沉默或过表达分析，以表明SEL1L和HRD1参与未组装的Ig-μ(s)的降解，但对另一种底物TCR-α的影响较小。SEL1L和HRD1定位于早期分泌装置，并在ER应激期间以及B细胞分化过程中，与大量IgM分泌的开始同时被诱导。这些发现揭示了SEL1L和HRD1在IgM质量控制中的作用。
