Mechanisms Determining the Morphology of the Peripheral ER

SummaryThe endoplasmic reticulum (ER) consists of the nuclear envelope and a peripheral network of tubules and membrane sheets. The tubules are shaped by the curvature-stabilizing proteins reticulons and DP1/Yop1p, but how the sheets are formed is unclear. Here, we identify several sheet-enriched membrane proteins in the mammalian ER, including proteins that translocate and modify newly synthesized polypeptides, as well as coiled-coil membrane proteins that are highly upregulated in cells with proliferated ER sheets, all of which are localized by membrane-bound polysomes. These results indicate that sheets and tubules correspond to rough and smooth ER, respectively. One of the coiled-coil proteins, Climp63, serves as a “luminal ER spacer” and forms sheets when overexpressed. More universally, however, sheet formation appears to involve the reticulons and DP1/Yop1p, which localize to sheet edges and whose abundance determines the ratio of sheets to tubules. These proteins may generate sheets by stabilizing the high curvature of edges.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (272 K)Download as PowerPoint slideHighlights► ER sheets are formed by edge stabilization through curvature-generating proteins ► Climp63 regulates the area and luminal width of ER sheets in mammalian cells ► ER sheets are enriched in translocon components and functionally signify rough ER ► Membrane-bound polysomes concentrate rough ER proteins to sheets