Matriptase-2 (TMPRSS6) is a member of the type II transmembrane serine protease (TTSP) family with an unknown pathophysiological function. Predominantly located at the surface of liver cells, higher mRNA levels have also been found in breast and prostate cancer tumours in human and mice models e.g. 4T1indicating that this enzyme, similar to other TTSPs, will likely have important cell surface associated roles in normal and disease states.
Recently it has been suggested that protein fragments, generated by cell surface matriptase-2 are able to modulate the iron balance and in an “über”-active state can lead to anemia, making matriptase-2 an essential regulator of iron homeostasis through its generation of novel signalling peptides. To confirm these suggestions we are using liver tissue extracts from Matriptase2 deficient and healthy wild-type mice for proteomic TAILS (Terminal Amine Isotopic Labeling of Substrate) and transcriptomic (CLIP-CHIP microarray) analysis to identify potential new substrates of matriptase-2.
We predict these approaches will identify the mechanisms by which matriptase-2 influences and regulates iron homeostasis and so might lead to the development of new therapeutics for iron deficiency and toxicity treatment.