ER Membrane, Protein Processing, and Membrane Contact Sites (MCSs)

Vocabulary flashcards focusing on the structure and functions of the ER membrane, N-linked oligosaccharide processing, protein folding and dislocation, and ER membrane contact sites (MCSs).

Endoplasmic Reticulum (ER) Membrane

The membrane surrounding the largest organelle in eukaryotic cells, which extends from the nuclear envelope throughout the cytoplasm and functions in protein and lipid synthesis, processing, and transport.

Rough ER

A region of the endoplasmic reticulum characterized by ribosomes attached to its cytoplasmic surface, responsible for synthesizing glycoproteins and carrying out post-translational modifications.

Smooth ER

A region of the endoplasmic reticulum involved in lipid and carbohydrate synthesis, including the production of phospholipids and cholesterol for cell membranes.

Dolichol Phosphate

A hydrophobic polyisoprenoid lipid containing $75\text{-}95$ carbon atoms embedded in the ER membrane, serving as the carrier upon which a $14\text{-residue}$ N-linked oligosaccharide precursor is preformed.

N-linked Oligosaccharide Precursor Transfer

The transfer of a preformed $\text{Glc}_3\text{Man}_9(\text{GlcNAc})_2$ precursor from dolichol to asparagine residues in a tripeptide sequence ($\text{Asn-X-Ser} / \text{Asn-X-Thr}$) as a new protein enters the ER lumen.

BiP (GRP78)

An ER chaperone protein that transiently binds to hydrophobic regions of newly synthesized proteins entering the ER to prevent premature folding into incorrect conformations.

Calnexin and Calreticulin

ER carbohydrate-binding lectins that bind to sugars on $7\text{ N-linked}$ oligosaccharide chains, pulling on sugars to prevent premature protein misfolding.

Protein Disulfide Isomerase (PDI)

An ER enzyme that catalyzes the formation of $6$ disulfide bonds per monomer to facilitate proper protein folding.

Dislocation

A quality control pathway in which misfolded secretory proteins in the ER lumen are recognized by specific ER membrane proteins and exported to the cytosol for degradation.

Membrane Contact Sites (MCSs)

Specialized intracellular domains where ER membranes come into close contact ($3\text{-}15\text{ nm}$ for ER-endosomes, $6\text{-}15\text{ nm}$ for ER-mitochondria) with other organelles without fusing.

Molecular Motors at MCSs

Kinesin-1 and Dynein molecular motors used along microtubules by both the ER and partner organelles to coordinate movement and drag ER tubules during trafficking.

ORP1L

An oxysterol-binding protein-related protein on late endosomes that senses cholesterol; it promotes inward movement under high cholesterol via RAB7-RILP-dynein or binds ER-resident VAP proteins under low cholesterol to retain endosomes at the periphery.

Protrudin

An ER membrane adaptor protein encoded by ZFYVE27 (ZFVVE27) that interacts with late endosomes via RAB7 and PtdIns(3)P, transferring Kinesin-1 to FYCO1 to promote outward movement to the cell periphery.

Hereditary Spastic Paraplegia (HSP)

A neurological disorder caused by mutations in the ZFYVE27 gene, affecting Protrudin function and ER morphology regulation.

Lipid Transfer Proteins (LTPs)

Specialized protein families (such as ORP, START, and Smp) that transfer non-vesicular lipids at MCSs by extracting, shielding, bridging, and inserting lipid molecules between membranes.

Mitochondrial Fission at ER Contacts

A process where ER tubules wrap around and constrict mitochondria, recruit actin-myosin complexes via INF2, and facilitate the assembly of the fission protein DRP1 (Dnm1 in yeast).

FAM21

A WASH complex component that colocalizes with the ER at endosome fission sites where endosomal cargoes are sorted between vacuolar and budding domains.

GRP75

A chaperone protein that couples ER $\text{Ins}(1,4,5)\text{P}_3$ receptors to outer mitochondrial VDACs, enhancing targeted $\text{Ca}^{2+}$ transfer into mitochondria.

EGFR-PTP1B Complex

An ER-endosome protein complex located at membrane contact sites that regulates EGFR signaling through dephosphorylation.

Niemann-Pick Type C Disease

A neurodegenerative disorder linked to membrane contact site dysfunction involving defective cholesterol export from endosomes.