Peripheral ER structure and function
Introduction
The endoplasmic reticulum (ER) has a complex structure with three main morphologically distinct regions that can be easily discriminated by fluorescence microscopy: firstly, the sheets of the nuclear envelope (NE); secondly, an extensive network of interconnected peripheral ER tubules; and thirdly, peripheral ER sheets (see Figure 1a). All three of these structural regions exist within the continuous membrane bilayer and therefore must be maintained by proteins that partition as they generate these ER domains [1]. Many mechanisms go into shaping the NE around nuclear contents and the details of this process have been previously reviewed [2]. This review will instead focus on the current knowledge of the structural and functional organization of the peripheral ER throughout the cell cycle. Recent work has revealed new factors that contribute to peripheral ER structure by directly shaping the membrane bilayer. This structure is highly conserved and contributes to ER functions [3]. The cytoskeleton interacts with the peripheral ER membrane to spread it throughout the cytoplasm and make the ER an incredibly dynamic organelle. By spreading the peripheral ER membrane throughout the cytoplasm into a complex and continuous network, the ER can physically and functionally associate with other membrane-bound compartments. Some of the proteins involved in these contact sites between the ER and other membranes have now been identified and their disruption affects both ER structure and function.
Section snippets
Factors that generate distinct ER shapes in different ER domains
The peripheral ER includes all regions of the ER other than the membrane sheets of the NE. The peripheral ER branches out of the NE as an extensive network of interconnected tubules and sheets that share a single lumen (see Figure 1a). The elaborate network of ER tubules is perhaps the most distinguishing feature of the peripheral ER (see Figure 1b). It has a much more complex structure than the flat sheets of the NE and not surprisingly is enriched in proteins that shape membranes into tubules
Peripheral ER structure during mitosis
The ER/NE membranes undergo large structural and functional changes during mitosis to allow redistribution of this organelle and its associated proteins to daughter cells. In yeast, the NE does not disassemble to the degree that it does in animal cells. In animal cells, the NE membrane fragments and the membrane and its associated proteins are absorbed into the peripheral ER, which does not disassemble to a significant degree in most cells [7•, 10••, 14, 15]. Elegant experiments in mammalian
The relationship between ER dynamics and the microtubule cytoskeleton
The peripheral ER is extremely dynamic and tracks along microtubules (MTs) in animal cells [19, 20, 21]. Even during interphase, the network of tubules and sheets is constantly rearranging and it is quite clear by live-cell imaging that tubular ER networks move along MT. The coalignment between growing ER tubules and MTs is visually perfect (see Figure 1c). In contrast, regions of the peripheral ER that are not dynamic do not coalign with MTs. In vitro systems also show that MTs are not
Functional interactions between the ER and other membrane systems
The ER has regions that appear in close association with nearly every other membrane-bound compartment in the cell including the mitochondria, peroxisomes, Golgi, vacuole, chloroplasts, and plasma membranes. These interactions have been shown in many cases to be functionally important and explain why the ER is organized into an extensive structure spread throughout the cytoplasm. The two main reasons for the ER to contact the membranes of other organelles are firstly, nonvesicular transport of
Conclusions
There are three main ways by which ER structure is determined that have been discussed: firstly, membrane proteins that partition within the membrane bilayer and directly shape it by forming oligomeric structures; secondly, interactions between membrane proteins on the ER and the cytoskeleton; and thirdly, interactions with other membrane-bound compartments. Much progress has been made, but still only a handful of the proteins that contribute to each of these three processes have been
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• Of special interest
•• Of outstanding interest
Acknowledgements
We thank Jonathan Friedman for careful reading of the manuscript and Brant Webster for providing images. This work was supported by the Searle Scholar Award to GKV and NIH grant RO1GM083977. AER and NZ were supported by an NIH training grant GM07135
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These authors contributed equally.