MembranMMPs

MembranMMPs, or membrane-type matrix metalloproteinases, are a subset of matrix metalloproteinases that are anchored to the plasma membrane and mediate pericellular proteolysis. They differ from secreted MMPs by their localization at the cell surface, which concentrates proteolytic activity near the cell and its microenvironment. Most MembranMMPs are either transmembrane proteins with a single-pass domain or glycosylphosphatidylinositol (GPI)-anchored proteins, enabling direct interaction with extracellular matrix and cell-surface receptors.

The best-characterized members include MMP-14 (MT1-MMP), MMP-15 (MT2-MMP), MMP-16 (MT3-MMP), MMP-17 (MT4-MMP), MMP-24 (MT5-MMP), and MMP-25 (MT6-MMP). They are synthesized as inactive zymogens and activated by proteolytic processing or interactions with other proteases. Once activated, MembranMMPs can directly degrade extracellular matrix components such as collagen and gelatin, and they can also activate other pro-MMPs, notably pro-MMP-2, thus amplifying a pericellular proteolytic cascade.

MembranMMPs play critical roles in normal physiology and development, including tissue remodeling, wound healing, and angiogenesis. They also contribute to pathological processes such as cancer cell invasion and metastasis, arthritis, and fibrosis. Activity regulation is multifaceted and includes inhibition by TIMPs, subcellular localization, endocytic trafficking, and interactions with cell-surface receptors and matrix co-factors, ensuring controlled proteolysis at the cell boundary.

In research and medicine, MembranMMPs are studied as mediators of tumor invasion, contributors to tissue regeneration, and potential therapeutic targets. Experimental approaches include genetic models, selective inhibitors, and activity-based probes to monitor focal proteolysis at the cell surface.