The trans-SNARE complex VAMP4/Stx6/Stx7/Vti1b is a key regulator of Golgi to late endosome MT1-MMP transport in macrophages.

The activity of the matrix metalloproteinase (MMP) MT1-MMP is strictly regulated by expression and cellular location. In macrophages LPS activation leads to the up-regulation of MT1-MMP and this need to be at the cell surface for them to degrade the dense extracellular matrix (ECM) components to create a path to migrate into injured and infected tissues. Fixed and live imaging shows newly made MT1-MMP is packaged into vesicles that traffic to and fuse with LBPA+ LAMP1+ late endosomes en route to the surface. The R-SNARE VAMP4, found on Golgi-derived vesicles that traffic to late endosomes, forms a trans-SNARE complex with the Q-SNARE complex Stx6/Stx7/Vti1b. The Stx6/Stx7/Vti1b complex has been shown to be up-regulated in lipopolysaccharide (LPS)-activated cells to increase trafficking of key cytokines through the classical pathway and now we show here it is up-regulation also plays a role in the late endosomal pathway of MT1-MMP trafficking. Depletion of any of the SNAREs in this complex reduces surface MT1-MMP and gelatin degradation. Conversely, overexpression of the Stx6/Stx7/Vti1b components increases surface MT1-MMP levels. This suggests that Stx6/Stx7/Vti1b is a key Q-SNARE complex in macrophages during an immune response and in partnership with VAMP4 it regulates transport of newly made MT1-MMP.

Development and use of biomaterials as wound healing therapies.

There is a vast number of treatments on the market for the management of wounds and burns, representing a multi-billion dollar industry worldwide. These include conventional wound dressings, dressings that incorporate growth factors to stimulate and facilitate the wound healing process, and skin substitutes that incorporate patient-derived cells. This article will review the more established, and the recent advances in the use of biomaterials for wound healing therapies, and their future direction.