Endoplasmic reticulum structure and interconnections with other organelles.

The endoplasmic reticulum (ER) is a large, continuous membrane-bound organelle comprised of functionally and structurally distinct domains including the nuclear envelope, peripheral tubular ER, peripheral cisternae, and numerous membrane contact sites at the plasma membrane, mitochondria, Golgi, endosomes, and peroxisomes. These domains are required for multiple cellular processes, including synthesis of proteins and lipids, calcium level regulation, and exchange of macromolecules with various organelles at ER-membrane contact sites. The ER maintains its unique overall structure regardless of dynamics or transfer at ER-organelle contacts. In this review, we describe the numerous factors that contribute to the structure of the ER.

Rab10 GTPase regulates ER dynamics and morphology.

We have identified Rab10 as an ER-specific Rab GTPase that regulates ER structure and dynamics. We show that Rab10 localizes to the ER and to dynamic ER-associated structures that track along microtubules and mark the position of new ER tubule growth. Rab10 depletion or expression of a Rab10 GDP-locked mutant alters ER morphology, resulting in fewer ER tubules. We demonstrate that this defect is due to a reduced ability of dynamic ER tubules to grow out and successfully fuse with adjacent ER. Consistent with this function, Rab10 partitions to dynamic ER-associated domains found at the leading edge of almost half of all dynamic ER tubules. Interestingly, this Rab10 domain is highly enriched with at least two ER enzymes that regulate phospholipid synthesis, phosphatidylinositol synthase (PIS) and CEPT1. Both the formation and function of this Rab10/PIS/CEPT1 dynamic domain are inhibited by expression of a GDP-locked Rab10 mutant. Together, these data demonstrate that Rab10 regulates ER dynamics and further suggest that these dynamics could be coupled to phospholipid synthesis.

Peripheral ER structure and function.

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.