Peripheral ER structure and function

Abstract

The endoplasmic reticulum (ER) is a single continuous membrane-enclosed organelle made up of functionally and structurally distinct domains. The ER domains include the nuclear envelope (NE) and the peripheral ER, which is a network of tubules and sheets spread throughout the cytoplasm. The structural organization of the ER is related to its many different cellular functions. Here we will discuss how the various functional domains of the peripheral ER are organized into structurally distinct domains that exist within the continuous membrane bilayer throughout the cell cycle. In addition, we will summarize our current knowledge on how peripheral ER membranes contact various other regions of the cytoplasm including the cytoskeleton, mitochondria, Golgi, and the plasma membrane and what is known about the functions of these interactions.

Figure 1

The structure of the ER. A) A mammalian COS cell fluorescently labeled with GFP-tagged Sec61β outlines morphologically distinct regions of the ER including the nuclear envelope (NE), peripheral ER sheets (S) and tubules (T). Also see close up image of tubules in (B). (C) peripheral ER in COS cells fluorescently labeled with cherry-Tubulin (red) and GFP-Sec61β (green) shows ER tubule tip (green arrow) tracking with growing MT tip (red arrow) by TAC mechanism. Part A was reproduced with permission from Nature Publishing Group. Images in parts B and C were kindly provided by Brant Webster.

Figure 2

Resident ER proteins utilized by the cell to shape ER membrane and link it to other regions within the cytoplasm. Reticulon (blue shapes) and DP1/Yop1 proteins shape the tubular ER and p180 (brown circle), polyribosomes (black tracks) and components of the translocon complex (Sec61β-turquoise circle) shape the sheet-like ER, and the inner and outer membranes of the nuclear envelope are linked by the LINC complex (pink and red rectangles). The peripheral ER has numerous contact points with various membranes. The ER proteins form bridges with the mitochondria through MFN2/MFN1 dimers (pink and purple circles), with Golgi membranes through VAPs (gray circles) interacting with lipid transfer binding proteins (LTBP- bright blue circles), and the plasma membrane potentially through Osh proteins (gold shape, sterols are green circles).