receptorKDEL

receptorKDEL, also known as the KDEL receptor (KDELR), is a family of endoplasmic reticulum retrieval receptors that recognize the C-terminal KDEL motif of soluble luminal ER resident proteins. They mediate the retrograde transport of escaped ER residents from the Golgi apparatus back to the endoplasmic reticulum, preserving ER luminal proteostasis. In mammals, several paralogs exist (KDELR1, KDELR2, KDELR3) with overlapping expression patterns; KDELR homologs are found across diverse eukaryotes, reflecting a conserved retrieval mechanism. The receptor is a seven‑transmembrane protein localized primarily to Golgi membranes, with dynamic cycling to the ER.

Mechanism and chemistry: KDELRs bind KDEL-containing cargo in the Golgi where the lumen is relatively acidic and release cargo in the neutral pH of the ER. Binding triggers recruitment of COPI coat proteins, facilitating retrograde vesicle formation and transport back to the ER. The cytosolic tail contains motifs that interact with the COPI machinery, enabling efficient retrieval. In yeast, receptors can recognize related signals such as HDEL, indicating a conserved family of retrieval receptors with species-specific preferences.

Cargo recognition: the primary ligand is the KDEL sequence at the C-terminus of soluble ER residents like chaperones and soluble enzymes. Some variants (e.g., HDEL) are recognized by KDELRs in other organisms, illustrating a balance between specificity and flexibility in cargo selection.

Biological significance: receptorKDEL maintains ER protein composition, prevents loss of luminal proteins during trafficking, and supports proper folding environments. Disruption of KDELR function can perturb ER homeostasis and secretory pathway efficiency, contributing to cellular stress and disease-related phenotypes in experimental models.

Nomenclature: KDELR1, KDELR2, KDELR3 refer to vertebrate paralogs; the term receptorKDEL serves as a general descriptor for the family.