Capture and delivery of tail-anchored proteins to the endoplasmic reticulum

• Published in: The Journal of cell biology Vol. 220; no. 8; p. 1
• Main Authors: Farkas, Ákos, Bohnsack, Katherine E
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 02.08.2021
• Subjects: Animals; Endoplasmic reticulum; Endoplasmic Reticulum - metabolism; Evolution, Molecular; Humans; Intracellular Membranes - metabolism; Membrane and Lipid Biology; Membrane Proteins - metabolism; Membranes; Mitochondria; Molecular Chaperones - metabolism; Protein Homeostasis; Protein Transport; Proteins; Quality control; Review; Ribosomes - metabolism; Saccharomyces cerevisiae - metabolism; Saccharomyces cerevisiae Proteins - metabolism; Selectivity; Signal Recognition Particle - metabolism; Yeasts
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.202105004

Tail-anchored (TA) proteins fulfill diverse cellular functions within different organellar membranes. Their characteristic C-terminal transmembrane segment renders TA proteins inherently prone to aggregation and necessitates their posttranslational targeting. The guided entry of TA proteins (GET in yeast)/transmembrane recognition complex (TRC in humans) pathway represents a major route for TA proteins to the endoplasmic reticulum (ER). Here, we review important new insights into the capture of nascent TA proteins at the ribosome by the GET pathway pretargeting complex and the mechanism of their delivery into the ER membrane by the GET receptor insertase. Interestingly, several alternative routes by which TA proteins can be targeted to the ER have emerged, raising intriguing questions about how selectivity is achieved during TA protein capture. Furthermore, mistargeting of TA proteins is a fundamental cellular problem, and we discuss the recently discovered quality control machineries in the ER and outer mitochondrial membrane for displacing mislocalized TA proteins.