ABSTRACT
T ail-anchored (TA) proteins are a heterogeneous group o f transmembrane proteins with diverse im portant functions that share an unusual mechanism o f insertion into their target membranes. Indeed, because o f the C-term inal position o f their transmembrane domain they do not have a chance to interact cotranslationally with Signal Recognition Particle and are thus delivered posttranslationally to the ER , to the outer mitochondrial-or to the peroxisomal membrane (as well as to the chloroplast outer envelope in plants). The subsequent insertion in volves translocation o f the C-terminus, however, TA proteins do not rely on the classical Sec61 translocon nor on the T O M machinery for their integration into the E R and outer m itochon drial m embrane respectively. Recent work has dem onstrated the existence o f different biogenetic pathways for TA proteins. Notably, some are able to efficiendy translocate their C-term inus across protein-free bilayers without the participation o f any membrane or cytosolic protein, while others require assistance from cytosolic chaperons and membrane receptors. W hether or not assistance is required depends on features o f the transmembrane domain. Several intriguing issues in TA protein biogenesis remain to be resolved and will undoubtedly be actively investigated in the com ing years. These include the molecular characterization o f the E R membrane receptors involved in the assisted pathway and the mechanism by which TA proteins discriminate between the outer m itochondrial membrane and the ER .
