Stress-induced retrotranslocation of clusterin/ApoJ into the cytosol. - Université de Rennes Accéder directement au contenu
Article Dans Une Revue Traffic Année : 2007

Stress-induced retrotranslocation of clusterin/ApoJ into the cytosol.

Résumé

Clusterin is a usually secreted glycoprotein with chaperone properties. Recently, it has been suggested that clusterin isoforms reside in the nuclear and cytosolic compartments of human cell types, where they can influence various cellular programs including DNA repair, transcription and apoptosis. Several mechanisms have been proposed to explain this atypical location, including alternative transcription initiation and alternative splicing. However, none of these have been unequivocally established as occurring in live cells. Here we provide direct experimental evidence that in live intact cells, under certain stress conditions, clusterin can evade the secretion pathway and reach the cytosol. This was demonstrated using several complementary approaches. Flow cytometry and selective permeabilization of U251 cell membranes with digitonin allowed detection of cytosolic clusterin in stressed U251 cells. In addition, a stringent enzymatic assay reliant upon the exclusively cytosolic deubiquitinase enzymes confirmed that clusterin synthesized with its hydrophobic secretion signal sequence can reach the cytosol of U251 cells. The retrotranslocation of clusterin is likely to occur through a mechanism similar to the endoplasmic reticulum (ER)-associated protein degradation pathway and involves passage through the Golgi apparatus. We also report that the ER-associated ubiquitin ligase Hrd1/synoviolin can interact with, and ubiquitinate clusterin. The possible biological functions of these novel behaviours of clusterin are discussed.

Dates et versions

hal-00149383 , version 1 (25-05-2007)

Identifiants

Citer

Philippe Nizard, Susanne Tetley, Yves Le Dréan, Tanguy Watrin, Pascale Le Goff, et al.. Stress-induced retrotranslocation of clusterin/ApoJ into the cytosol.. Traffic, 2007, 8 (5), pp.554-65. ⟨10.1111/j.1600-0854.2007.00549.x⟩. ⟨hal-00149383⟩
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