The sorting protein PACS-2 promotes ErbB signalling by regulating recycling of the metalloproteinase ADAM17

The metalloproteinase ADAM17 activates ErbB signalling by releasing ligands from the cell surface, a key step underlying epithelial development, growth, and tumour progression. However, mechanisms acutely controlling ADAM17 cell-surface availability to modulate the extent of ErbB ligand release are poorly understood. Here, through a functional genome-wide siRNA screen, we identify the sorting protein PACS-2 as a regulator of ADAM17 trafficking and ErbB signalling. PACS-2 loss reduces ADAM17 cell-surface levels and ADAM17-dependent ErbB ligand shedding, without apparent effects on related proteases. PACS-2 co-localizes with ADAM17 on early endosomes and PACS-2 knockdown decreases the recycling and stability of internalized ADAM17. Hence, PACS-2 sustains ADAM17 cell-surface activity by diverting ADAM17 away from degradative pathways. Interestingly, Pacs2-deficient mice display significantly reduce

Orbital Implants and Wrapping Materials

Following globe removal, the surgeon must determine the best orbital implant to place into the anophthalmic socket. A decision on appropriate implant size, whether to place a porous or nonporous implant, and a patient’s total clinical picture must be considered to prevent future complications. Other considerations, including whether to wrap an implant and place a motility peg, must also be made. The modern implant is built on the foundation of anophthalmic socket reconstruction—implant retention, volume replacement, and adequate prosthetic motility. This chapter will review the special considerations the ophthalmic surgeon must weigh when choosing an orbital implant following enucleation and evisceration surgeries