Review Article

UPR-Mediated Membrane Biogenesis in B Cells

Figure 2

XBP1(S), lipids, and secretory pathway machinery in ER biogenesis. In activated B cells, we propose that increased demand for lipids as well as increased demand on the protein folding capacity of the ER promotes induction of the XBP1(S) transcriptional activator via the IRE1/XBP1 branch of the UPR. The means by which these demands are sensed by the IRE1/XBP1 pathway remain unclear. XBP1(S), via transcriptional control, upregulates expression of a large cohort of proteins involved in the synthesis, maturation, and transport of cargo proteins within the secretory pathway. Much of this secretory machinery localizes to the ER. XBP1(S), via mechanisms that are poorly understood, also drives lipid biosynthesis, including production of the major phospholipid PtdCho by the CDP-choline pathway. Thus, XBP1(S) coordinates mechanisms that supply both the lipid and protein components necessary for construction of the ER.
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