RESEARCH

Most eukaryotic proteins that function in the endomembrane system or extracellular space traverse the translocon during or shortly after translation. Proteins that arrest during translocation clog the channel, prevent the passage of other proteins into the endoplasmic reticulum (ER), and impair cell function. Underscoring the importance of maintaining functional translocons, eukaryotes possess multiple conserved translocon quality control (TQC) mechanisms, several of which we have discovered or characterized. Numerous proteins essential for health use the translocon as a portal to the endomembrane system. Enzymes mediating TQC promote neurological homeostasis, healthy aging, and other aspects of human health. At least two proteins with profound significance for metabolic physiology (low-density lipoprotein component apolipoprotein B and oligomeric islet amyloid polypeptide) persistently engage translocons. Components of conserved TQC mechanisms represent potential therapeutic targets for several human diseases, including hypercholesterolemia and diabetes. Our lab uses a combination of genetic and biochemical approaches in a yeast model system to characterize molecular mechanisms by which cells resolved clogged channels.