Rough endoplasmic reticulum
Reticulum endoplasmicum granulosum
Also known as: RER, rough ER, granular ER, ergastoplasm
A network of flattened membrane sacs (cisternae) studded with ribosomes, continuous with the outer nuclear membrane, where secretory, lysosomal and membrane proteins are made, folded and N-glycosylated.
Overview
Proteins destined for the secretory pathway carry an N-terminal signal sequence (≈15–30 mostly hydrophobic amino acids). As it emerges from the ribosome the signal recognition particle (SRP) binds it and pauses translation; SRP docks on its receptor in the ER membrane and hands the ribosome to the Sec61 translocon, through which the chain is threaded into the lumen as it is made (co-translational translocation; Blobel's signal hypothesis). Signal peptidase removes the signal; stop-transfer sequences instead anchor transmembrane proteins in the membrane.
In the lumen, proteins are folded with help from chaperones (BiP, calnexin and calreticulin), disulfide bonds are formed by protein disulfide isomerase, and a preformed 14-sugar oligosaccharide is transferred en bloc from dolichol phosphate to asparagine residues (N-linked glycosylation). Collagen chains are hydroxylated (prolyl and lysyl hydroxylases, vitamin C-dependent) and assembled into triple-helical procollagen here. Multi-subunit proteins are assembled before export.
Quality control: misfolded proteins are retained, then retro-translocated to the cytosol, ubiquitinated and destroyed by the proteasome (ER-associated degradation, ERAD). Accumulation of unfolded protein triggers the unfolded protein response (IRE1, PERK, ATF6), which reduces translation and increases chaperone production — or triggers apoptosis if stress persists. Correctly folded cargo leaves at ER exit sites in COPII-coated vesicles bound for the Golgi.
- Location
Cytoplasm, often surrounding the nucleus; its lumen is continuous with the perinuclear space of the nuclear envelope.
Anatomy
- Histology
Abundant RER makes cytoplasm intensely basophilic ("ergastoplasm"). Typical RER-rich cells: plasma cells (eccentric nucleus, clock-face chromatin, perinuclear Golgi "hof"), pancreatic acinar cells (basal basophilia), fibroblasts, osteoblasts, goblet cells, hepatocytes and neurons (Nissl bodies).
Function
- Synthesis of secreted, lysosomal, plasma-membrane and ER/Golgi proteins.
- Protein folding, disulfide-bond formation and assembly of multimers.
- Initial N-linked glycosylation.
- Quality control (ERAD, unfolded protein response).
- Post-translational modification of procollagen (hydroxylation, triple-helix formation).
Clinical significance
α1-Antitrypsin deficiency
The PiZ variant misfolds and polymerises in the hepatocyte RER: retained protein forms PAS-positive, diastase-resistant globules causing hepatitis and cirrhosis, while the lack of circulating inhibitor allows neutrophil elastase to destroy alveolar walls (panacinar emphysema).
Cystic fibrosis ΔF508
The mutant CFTR folds abnormally, is retained by ER quality control and degraded by ERAD, so little channel reaches the apical membrane. CFTR "correctors" (e.g. elexacaftor, tezacaftor) improve folding and trafficking.
Test yourself
In scurvy, collagen is weak because vitamin C is a cofactor for which reaction?
- Cleavage of procollagen propeptides
- Hydroxylation of proline and lysine residues in the rough ER
- Copper-dependent cross-linking by lysyl oxidase
- Glycosylation in the Golgi
Answer: Hydroxylation of proline and lysine residues in the rough ER
Prolyl and lysyl hydroxylases (in the RER) need ascorbate. Without hydroxyproline the triple helix is unstable; capillary fragility causes bleeding gums, perifollicular haemorrhages and poor wound healing.
Compiled from standard anatomy and physiology references — see the Cells & Tissues sources. For education only; not medical advice.