Endoplasmic reticulum

The endoplasmic reticulum (ER) is a major organelle found in most eukaryotic cells, forming an extensive internal membrane system essential for the synthesis, folding and transport of proteins and lipids. The term endoplasmic refers to its location within the cytoplasm, while reticulum, meaning “little net”, describes its characteristic interconnected network of membranes. The ER occurs in two forms—the rough endoplasmic reticulum (RER) and the smooth endoplasmic reticulum (SER)—which share structural continuity but differ markedly in function. Together, these systems support a wide range of cellular processes, particularly in cells with high secretory or metabolic activity.

Structural Organisation

The ER consists of a continuous membrane system that extends from the outer nuclear membrane into the cytoplasm. It forms flattened membrane-bound sacs known as cisternae in the RER and more tubular structures in the SER. The enclosed internal space, or lumen, is continuous with the perinuclear space but distinct from the cytosol. The ER network is supported by the cytoskeleton and is capable of structural reorganisation in response to cellular needs, including changes in membrane composition and the proportion of rough to smooth regions.
Although widespread among eukaryotic cells, the ER is absent from mature red blood cells and spermatozoa, which contain highly reduced cytoplasmic structures.

Historical Observations

The ER was first identified using light microscopy by Charles Garnier in 1897, who used the term ergastoplasm to describe its appearance. Its detailed membrane system was later resolved in 1945 through electron microscopy by Keith Porter, Albert Claude and Ernest Fullam, revealing the extensive membranous network now recognised as the ER.

Rough Endoplasmic Reticulum

The rough endoplasmic reticulum derives its name from its appearance under the microscope: the cytosolic surface is studded with ribosomes engaged in protein synthesis. These ribosomes attach transiently to membrane-bound protein complexes called translocons. A ribosome binds to the RER only when synthesising a protein destined for secretion, membrane insertion or residence within the endomembrane system.
The targeting process begins when the ribosome translates a signal peptide, typically encoded by the first several amino acids of the polypeptide. This signal is recognised by the signal recognition particle (SRP), which pauses translation and directs the ribosome to the RER membrane. Once bound to the translocon, translation resumes, feeding the nascent protein into the ER lumen or membrane. Signal peptides are cleaved by signal peptidases, and proteins undergo initial folding and modification.
One major modification is N-linked glycosylation, in which oligosaccharyltransferase adds a characteristic carbohydrate chain to asparagine residues within appropriate sequence motifs. This early quality-control step supports correct folding before proteins are packaged into vesicles for transport to the Golgi apparatus.
Structurally, RER membranes form stacked double-membrane sheets connected by helical structures known as Terasaki ramps, creating a highly organised three-dimensional network. Proteins synthesised in the RER are transported primarily by COPII-coated vesicles to the Golgi apparatus, while COPI-coated vesicles mediate retrograde transport. Additional exchange occurs through membrane contact sites, which permit direct lipid transfer between organelles.
The RER is especially abundant in cells engaged in extensive protein synthesis, such as hepatocytes and secretory cells.

Smooth Endoplasmic Reticulum

The smooth endoplasmic reticulum lacks ribosomes and performs distinct metabolic functions. It forms a branching tubular network often situated near the cell periphery, with its morphology adapted to support varied biochemical roles. In many cells, smooth and rough regions merge at transitional ER sites where transport vesicles bud off toward the Golgi apparatus.
Key functions of the SER include:

• Lipid and phospholipid synthesis, providing essential components for cellular membranes.
• Steroid hormone production, particularly in endocrine tissues such as the testes, ovaries and adrenal glands.
• Detoxification of metabolic by-products, alcohol and xenobiotics, especially pronounced in liver cells.
• Carbohydrate metabolism, including the final step of gluconeogenesis via glucose-6-phosphatase.
• Calcium regulation, especially in excitable cells.

In muscle cells, a specialised form of SER known as the sarcoplasmic reticulum (SR) plays a crucial role in excitation–contraction coupling. It stores high concentrations of calcium ions and releases them into the sarcoplasm upon stimulation, triggering interaction between contractile proteins that drive muscle contraction. Subsequent calcium reuptake resets the system for the next contraction cycle.

Functional Integration

The ER is central to the intracellular transport of proteins and lipids. Proteins folded and modified within the RER are packaged into vesicles and directed to the Golgi apparatus, where they undergo further processing and sorting. The ER also synthesises membrane lipids, contributing to the continual renewal of cellular and organelle membranes.
Beyond biosynthetic roles, the ER participates in:

• Protein quality control, including the detection and correction or degradation of misfolded proteins.
• Calcium homeostasis, influencing signalling pathways.
• Detoxification processes through enzymatic pathways concentrated in the SER.