Multivesicular body formation enhancement and exosome release during endoplasmic reticulum stress

• Published in: Biochemical and biophysical research communications 2016-11, Vol.480 (2), p.166-172
• Main Authors: Kanemoto, Soshi, Nitani, Ryota, Murakami, Tatsuhiko, Kaneko, Masayuki, Asada, Rie, Matsuhisa, Koji, Saito, Atsushi, Imaizumi, Kazunori
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; eIF-2 Kinase - metabolism; ELECTRON MICROSCOPY; ENDOPLASMIC RETICULUM; Endoplasmic Reticulum Stress - physiology; Endoribonucleases - metabolism; Exosome; Exosomes - metabolism; HeLa Cells; Humans; IRE1; Multivesicular Bodies - physiology; Multivesicular body; PERK; Protein-Serine-Threonine Kinases - metabolism; Signal Transduction; STRESSES
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2016.10.019

The endoplasmic reticulum (ER) plays a pivotal role in maintaining cellular homeostasis. However, numerous environmental and genetic factors give rise to ER stress by inducing an accumulation of unfolded proteins. Under ER stress conditions, cells initiate the unfolded protein response (UPR). Here, we demonstrate a novel aspect of the UPR by electron microscopy and immunostaining analyses, whereby multivesicular body (MVB) formation was enhanced after ER stress. This MVB formation was influenced by inhibition of ER stress transducers inositol required enzyme 1 (IRE1) and PKR-like ER kinase (PERK). Furthermore, exosome release was also increased during ER stress. However, in IRE1 or PERK deficient cells, exosome release was not upregulated, indicating that IRE1- and PERK-mediated pathways are involved in ER stress-dependent exosome release. •Endoplasmic reticulum (ER) stress induces multivesicular body (MVB) formation.•ER stress transducers IRE1 and PERK mediate MVB formation.•Exosome release is enhanced after ER stress.•IRE1 or PERK deficiency blocks upregulation of ER stress-dependent exosome release.