Targeting and surveillance mechanisms for tail-anchored proteins

Tail-anchored (TA) proteins are single-pass transmembrane proteins, which contain cytosolic domains and a C-terminal transmembrane domain (TMD) anchored to organelle membranes, leaving a short tail within the lumen of organelles. Organelle specific insertion pathways exist to establish TA proteins targeting specificity. Additionally, surveillance mechanisms contribute to targeting specificity by clearing mis-targeted TA proteins. Cytosolic quality control pathways clearmis-targeted TA proteins from cytosol. MSP1 and ATP13A1/CATP-8/Spf1 extract mis-targeted TA proteins from mitochondria and ER, respectively. Here, we review the progress on the targeting and clearance mechanisms of TA proteins with a focus on ER and mitochondria proteins.