Fig 1. Insulin biosynthesis.

Schematic representation of proinsulin synthesis, followed by either secretion or degradation. (1) Proinsulin molecules co-translationally translocate into the ER lumen. (2) Properly folded proinsulin molecules traffic to the secretory granules. Misfolded or abundant proinsulin molecules dislocate across the ER membrane (3) into the cytosol, potentially assisted by HRD1, Derlin-1 or Derlin-2 and p97 (inset). Cytosolic proinsulin is then degraded into smaller peptides by the proteasome. Proinsulin derived peptides are reimported into the ER lumen via TAP and (4) loaded onto MHC class I molecules. These traffic to the plasma membrane and (5) present the proinsulin-derived peptides to CD8⁺ T-cells.