The Ways of Tails: the GET Pathway and more

The Biogenesis of Mitochondrial Outer Membrane Proteins Show Variable Dependence on Import Factors

“…Such an alternative route might involve a yet unknown protein factor or the lipid core of the membrane as it was reported that the optimal integration of helical proteins into the MOM requires low ergosterol content and the presence of cardiolipin and phosphatidic acid (Kemper et al, 2008;Sauerwald et al, 2015;Vogtle et al, 2015). A similar multi pathway scenario is also discussed for the membrane integration of TA proteins into the ER membrane where at least four, partially overlapping, potential pathways are postulated (Borgese et al, 2019).…”

Guiding tail-anchored membrane proteins to the endoplasmic reticulum in a chaperone cascade

“…The past decade has witnessed the discovery of several pathways that mediate the targeted delivery and insertion of TAs, including the GET-, SND-, and EMC-dependent pathways (Fig. 1) (2,6,13,16,20,21,23). The GET pathway, which targets relatively hydrophobic TAs to the ER, is especially well-studied.…”

“…In the past decade, an increasing number of factors have been described that represent components of multiple, distinct protein-targeting pathways that deliver nascent membrane proteins to diverse organelles such as the endoplasmic reticulum (ER), mitochondria, and peroxisomes (1)(2)(3)(4)(5)(6). One of these pathways, the guided entry of tail-anchored protein (GET) pathway, has been studied in exquisite mechanistic detail.…”

Hydrogenosomal tail-anchored proteins are targeted to both mitochondria and ER upon their expression in yeast cells

“…These proteins can be inserted into ER, mitochondrial, or peroxisomal membrane, and expose the large soluble domain towards the cytosol. Since the TMS, which contains the targeting information, is the last portion of the polypeptide to be released from the ribosome, TA proteins can be imported only post-translationally [9]. The physicochemical properties of the TMS and its flanking regions seem to dictate the target organelle for these proteins.…”

“…ER TA proteins generally have longer and more hydrophobic TMS, while mitochondrial proteins are characterized by shorter and less hydrophobic TMS, flanked by positively charged residues on both sides. Finally, low hydrophobicity of the TMS, coupled with basic residues at the C-terminal element (CTE) directs TA proteins to peroxisomes [9,10]. An additional feature, which seems to influence the targeting of TA proteins, is the helical content.…”