title: Spatial separation of Golgi and ER during mitosis protects SREBP from unregulated activation.
abstract: Sterol regulatory element-binding proteins (SREBPs) are membrane-bound transcription factors that reside as inactive precursors in the endoplasmic reticulum (ER) membrane. After sterol depletion, the proteins are transported to the Golgi apparatus, where they are cleaved by site-1 protease (S1P). Cleavage releases the active transcription factors, which then enter the nucleus to induce genes that regulate cellular levels of cholesterol and phospholipids. This regulation depends on the spatial separation of the Golgi and the ER, as mixing of the compartments induces unregulated activation of SREBPs. Here, we show that S1P is localized to the Golgi, but cycles continuously through the ER and becomes trapped when ER exit is inhibited. During mitosis, S1P is associated with mitotic Golgi clusters, which remain distinct from the ER. In mitotic cells, S1P is active, but SREBP is not cleaved as S1P and SREBP reside in different compartments. Together, these results indicate that the spatial separation of the Golgi and the ER is maintained during mitosis, which is essential to protect the S1P substrate SREBP from unregulated activation during mitosis.
authors.affiliation: Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9039, USA.
authors.forename: René
authors.initials: R
authors.lastname: Bartz
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Sun
authors.forename: Blaine
authors.initials: B
authors.lastname: Bisel
authors.forename: Jen-Hsuan
authors.initials: JH
authors.lastname: Wei
authors.forename: Joachim
authors.initials: J
authors.lastname: Seemann
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D004789:Enzyme Activation; D006056:Golgi Apparatus / Q000201:enzymology / Q000378:metabolism*; D006801:Humans; D008938:Mitosis; D043484:Proprotein Convertases / Q000378:metabolism; D021381:Protein Transport; D051381:Rats; D012697:Serine Endopeptidases / Q000378:metabolism; D051779:Sterol Regulatory Element Binding Proteins / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D051779:Sterol Regulatory Element Binding Proteins; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; C115575:membrane-bound transcription factor peptidase, site 1