Reticulon 3 mediates Bcl-2 accumulation in mitochondria in response to endoplasmic reticulum stress.
Reticulon3 (RTN3), firstly isolated from the retina and widely expressed in human tissues with the highest expression in the brain, is presumed to play an important role in the developing axons through the transport of liquids and proteins. We have identified and characterized RTN3 as a RTN4B/ASY interaction protein. Here we demonstrated that ER-stress activated RTN3 expression. CHOP and ATF6 were sufficient to up-regulate the expression of RTN3. The down-regulation of RTN3 would induce apoptosis and attenuate the anti-apoptotic activity of Bcl-2, indicating RTN3 was required for the cellular survival and optimal anti-apoptotic activity of Bcl-2. Our present studies also indicated ER-stress induced RTN3 up-regulation could trigger Bcl-2 translocation from ER to mitochondria. Moreover, the previous studies showed that RTN4B was also a Bcl-2-interacted protein. We found that RTN3 and RTN4B could block the access of Bcl-2 to each other and thereafter determined the Bcl-2 subcellular distribution. Taken together, our findings indicate that RTN3 is directly involved in the ER-constituents trafficking events through dually acting as an essential and important ER-stress sensor, and a trigger for the Bcl-2 translocation.
Wan
Qingwen
Q
The National Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan, Hubei, 430072, People's Republic of China.
Kuang
Ersheng
E
Dong
Wei
W
Zhou
Shumin
S
Xu
Hua
H
Qi
Yipeng
Y
Liu
Yingle
Y
D051702:Activating Transcription Factor 6 / Q000378:metabolism; D017209:Apoptosis; D001483:Base Sequence; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival; D004721:Endoplasmic Reticulum / Q000473:pathology*; D015870:Gene Expression; D006367:HeLa Cells; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007700:Kinetics; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D008969:Molecular Sequence Data; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000070798:Nogo Proteins; D011401:Promoter Regions, Genetic / Q000235:genetics; D011485:Protein Binding; D021381:Protein Transport; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
D051702:Activating Transcription Factor 6; D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009185:Myelin Proteins; D009419:Nerve Tissue Proteins; D000070798:Nogo Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; C476198:RTN3 protein, human; C000603199:RTN4 protein, human; D051742:Transcription Factor CHOP