Matriptase-2 (TMPRSS6): a proteolytic regulator of iron homeostasis

A. J. Ramsay, J. D. Hooper, A. R. Folgueras, G. Velasco, C. Lopez-Otin
2009 Haematologica  
Maintaining the body's levels of iron within precise boundaries is essential for normal physiological function. Alterations of these levels below or above the healthy limit lead to a systemic deficiency or overload in iron. The type-two transmembrane serine protease (TTSP), matriptase-2 (also known as TMPRSS6), is attracting significant amounts of interest due to its recently described role in iron homeostasis. The finding of this regulatory role for matriptase-2 was originally derived from the
more » ... observation that mice deficient in this protease present with anemia due to elevated levels of hepcidin and impaired intestinal iron absorption. Further in vitro analysis has demonstrated that matriptase-2 functions to suppress bone morphogenetic protein stimulation of hepcidin transcription through cell surface proteolytic processing of the bone morphogenetic protein co-receptor hemojuvelin. Consistently, the anemic phenotype of matriptase-2 knockout mice is mirrored in humans with matripase-2 mutations. Currently, 14 patients with iron-refractory iron deficiency anemia (IRIDA) have been reported to harbor various genetic mutations that abrogate matriptase-2 proteolytic activity. In this review, after overviewing the membrane anchored serine proteases, in particular the TTSP family, we summarize the identification and characterization of matriptase-2 and describe its functional relevance in iron metabolism.
doi:10.3324/haematol.2008.001867 pmid:19377077 pmcid:PMC2688576 fatcat:dv4uoy2h4fda3aqiwtszd5x36u