Post-translational protein targeting by the GET pathway

How post-translational protein targeting pathways escort hydrophobic membrane proteins to their correct target site is a fundamental mechanistic challenge. In the recently discovered Guided Entry of Tail-anchor (GET) pathway, seemingly ‘simple’ TA proteins are delivered to the ER by a puzzlingly complex cascade of protein interactions that revolves around the dimeric ATPase Get3. The GET pathway provides an excellent opportunity to probe post-translational mechanisms of protein targeting and address fundamental questions: How are hydrophobic membrane proteins effectively protected during post-translational modes of targeting? What provides spatiotemporal control of the complex series of molecular events in this pathway? What molecular signals direct TA proteins to distinct organelles in eukaryotic cells? How do distinct post-translational protein targeting pathways intersect with one another and with quality control machineries?

Selected Publications:

  • Rome ME, Rao M, Clemons WM Jr., and Shan SO. (2013) Proc. Natl. Acad. Sci. “Precise timing of ATPase activation drives targeting of tail-anchored proteins.” PMID: 23610396.
  • Chio US, Chung S, Weiss S*, and Shan SO. (2017) Proc. Natl. Acad. Sci. 114(41), E8585-E8594. “A protean clamp guides membrane targeting of tail-anchored proteins.” PMID: 28973888.
  • Cho H and Shan SO*. (2018) EMBO J. 37(16): e99264. “Substrate relay in an Hsp70-cochaperone cascade safeguards tail-anchored membrane protein targeting.” PMID: 29973361.
  • Chio US, Chung S, Weiss S, and Shan SO*. (2019) Cell Rep. 26(1): 37-44.e7. “A chaperone lid ensures efficient and privileged client transfer during tail-anchored protein targeting.” PMID: 30605684.