Membrane Insertion of Tail‐anchored Proteins

Abstract

Tail‐anchored (TA) proteins are a special class of transmembrane proteins, which harbour only a single hydrophobic segment adjacent to their most C ‐terminus. This anchor must be inserted into membranes posttranslationally to allow for their correct cellular localization. Although TA proteins have essential cellular roles such as signal transduction, apoptosis and vesicle fusion, their biogenesis route has for many years remained unknown. Recently, several advances have created a new understanding of the TA protein insertion machinery. Uncovering the machinery responsible for the biogenesis of TA proteins should further our ability to understand a wide variety of diseases such as forms of cancer caused by activation of the TA protein oncogene BCL2 . Key concepts: Tail‐anchored proteins have C ‐terminal hydrophobic domains. Tail‐anchored proteins are inserted posttranslationally into the membrane. The GET complex inserts tail‐anchored proteins into the endoplasmic reticulum membrane in yeast. The TRC complex chaperones tail‐anchored proteins into membranes in humans.

Ergosterol content specifies targeting of tail-anchored proteins to mitochondrial outer membranes

“…Despite the fact that TA proteins can be found on all organelles, their insertion into membranes seems to occur into either the mitochondrial outer membrane (MOM) or the endoplasmic reticulum (ER), which serve as the first station for TA proteins of all other compartments of the secretory pathway ( Schuldiner et al. , 2008 , 2010 ).…”