Selective activation of the transcription factor ATF6 mediates endoplasmic reticulum proliferation triggered by a membrane protein

摘要: It is well known that the endoplasmic reticulum (ER) capable of expanding its surface area in response both to cargo load and increased expression resident membrane proteins. Although load, as unfolded protein (UPR), characterized, mechanism has been unclear. As a model system investigate this phenomenon, we have used HeLa-TetOff cell line inducibly expressing tail-anchored construct consisting an N-terminal cytosolic GFP moiety anchored ER by tail cytochrome b5 [GFP-b(5)tail]. After removal doxycycline, GFP-b(5)tail expressed at moderate levels (1-2% total protein) that, nevertheless, induce proliferation, assessed EM three- fourfold increase phosphatidylcholine synthesis. We investigated possible participation each three arms UPR found only activating transcription factor 6 (ATF6) arm was selectively activated after induction expression; peak ATF6α activation preceded Surprisingly, up-regulation ATF6 target genes not observed under these conditions. Silencing abolished proliferation response, whereas knockdown Ire1 without effect. Because lacks luminal domain, observe unlikely originate from lumen. Instead, propose sensing operates within lipid bilayer trigger selective ATF6.