[Frontiers in Bioscience 12, 5060-5070, September 1, 2007]

Matriptase-dependent cell surface proteolysis in epithelial development and pathogenesis

Thomas H. Bugge, Karin List, Roman Szabo

Proteases and Tissue Remodeling Unit, National Institute of Dental and Craniofacial Research, National Institutes of Health, Bethesda, MD


1. Abstract
2. Introduction: identification of matriptase as a new epithelial membrane serine protease
3. Tissue localization of matriptase
3.1. Matriptase expression during embryogenesis
3.2. Postnatal matriptase expression
4. Physiological functions of matriptase
5. Pathogenesis of dysregulated matriptase activity
6. Perspectives
7. Acknowledgements
8. References


Matriptase is an epithelial type II transmembrane serine protease with a complex modular structure and sophisticated activation mechanism. Reduced matriptase activity in mice or humans is associated with incomplete terminal differentiation of epidermis, epidermal appendages, oral epithelium, and, likely, other epithelial structures. Preliminary evidence indicates that matriptase is part of a serine protease zymogen activation cascade that regulates epithelial cell proliferation and fate. Matriptase activity must be tightly controlled in epithelial tissues by transcriptional and posttranslational mechanisms, as matriptase dysregulation can cause embryonic demise as well as malignant transformation.