© 1999 Robert A. Freitas Jr. All Rights Reserved.

Robert A. Freitas Jr., Nanomedicine, Volume I: Basic Capabilities, Landes Bioscience, Georgetown, TX, 1999

8.5.3.5 Endoplasmic Reticulum

The endoplasmic reticulum (ER), the principal protein manufacturing facility of the cell (aside from free ribosomes), is the most spatially extensive cytoplasmic organelle (Fig. 8.39). The ER is an interconnecting membranous network of fluid-filled vesicles, branching tubules, and flattened sacs or cavities called cisternae, possessed by almost all eukaryotic cells. The 5-6 nm thick membrane of the endoplasmic reticulum typically constitutes more than half of the total membrane surface area present in a cell. The membranes enclose a space that is continuous throughout the network and connects with the perinuclear space between the two membranes of the nuclear envelope (Section 8.5.4.1), allowing transport of manufactured substances throughout the cell. The fluid occupying the luminal or cisternal space of the ER, which is typically 20-40 nm wide but ranges from 10-70 nm, is called the reticuloplasm. There are ER-specific luminal proteins called reticuloplasmins found only in the reticuloplasm⁹⁹⁹ -- if these proteins are detected, a nanorobot has localized its position uniquely to this space. For example, molecular chaperones that assist in protein folding and are unique to the ER lumen include immunoglobin heavychain binding protein (BiP) and calnexin.¹⁰⁸⁰ BiP bears the "KDEL" amino acid sequence (Lys-Asp-Glu-Leu) at its C-terminus, a tagging sequence specifying that a protein is intended for attachment to the luminal surface of the ER cisterna.⁹⁹⁶ There is evidence that specific compartments or subdomains within the ER may perform specialized functions and may also bear unique chemical markers,¹¹³⁸ thus allowing nanorobots to distinguish different regions of the ER.

There are two varieties of endoplasmic reticulum -- rough or "granular" ER, and smooth or "agranular" ER, both present in the same cell. One variety or the other may predominate in a given cell type depending on the specific functions performed by the cell, and the mix may change within the same cell during different periods of cell activity. Both are anchored to and mobilized by cytoskeletal motor proteins.

Rough ER is an extensive membranous network of flattened sheets with a flattened sac appearance and a continuous cisternal space that communicates directly with the perinuclear space. Ribosomes are bound to the ER membrane only on the cytosolic surface, loosely attached by short cylindrical conduits comprised of the Sec61 trimeric protein complex¹⁰²⁴ spanning the ER membrane and produced exclusively in the granular ER. Ribosome-produced proteins enter the cisternal space through these conduits, called translocons,¹⁰¹⁸ in the ER membrane. Found in all nucleated cells except sperm, rough ER synthesizes proteins and packages proteins destined to be secreted by cells. The rough ER is also the site of the initial steps in the addition of sugar groups to glycoproteins by dolichol, a hydrophobic lipid that resides in the ER membrane with its active group facing the ER lumen.⁹⁹⁷ Rough ER is especially abundant in cells that are specialized for protein secretion such as the pancreatic acinar cells and antibody-secreting plasma cells, or that are specialized for extensive membrane synthesis such as the immature egg cell or the retinal rod cell. In such cases, almost half of the total ribosomes present in the cell may be bound to the granular ER. Glycoproteins produced in the rough ER become encapsulated by bits of ER membrane, which bud off and migrate along cytoskeletal elements to the Golgi complex for further processing.

Smooth ER has a branched, tubular structure with no ribosomes on its surface, though its interior is continuous with the granular ER. Agranular ER has enzymes in the cisternal side of its membrane that allow it to synthesize carbohydrates, lipids (including neutral fats, phospholipids and steroids), and lipoproteins (in liver cells), and that allow it to assist in drug detoxification in the liver and kidney.⁹⁴⁰ Muscle cells have a specialized, elaborate smooth ER called the sarcoplasmic reticulum that sequesters Ca⁺⁺ (which controls muscle contraction) from the cytosol. Cells in the testes that synthesize steroid hormones from cholesterol have an expanded smooth ER compartment to accommodate enzymes needed to synthesize cholesterol and then to modify it to make steroid hormones.

Last updated on 20 February 2003