Matriptase and prostasin are expressed in human skin in an inverse trend over the course of differentiation and are targeted to different regions of the plasma membrane.

Chih-Hsin Lai,Jehng-Kang Wang,Eric B Berens,Michael D Johnson,Ying-Jun J Lai,Yi-Jie J Wang,Yen-Ju Chen,Chen-Yong Lin,Shun-Cheng Chang,Hsiang-Hua D Chang

doi:10.1242/bio.019745

Abstract

ABSTRACTMatriptase and prostasin, acting as a tightly coupled proteolytic cascade, were reported to be required for epidermal barrier formation in mouse skin. Here we show that, in human skin, matriptase and prostasin are expressed with an inverse pattern over the course of differentiation. Matriptase was detected primarily in epidermal basal keratinocytes and the basaloid cells in the outer root sheath of hair follicles and the sebaceous gland, where prostasin was not detected. In contrast, prostasin was detected primarily in differentiated cells in the epidermal granular layer, the inner root sheath of hair follicles, and the sebaceous gland, where matriptase expression is negligible. While co-expressed in the middle stage of differentiation, prostasin was detected as polarized patches, and matriptase at intercellular junctions. Targeting to different subcellular localizations is also observed in HaCaT human keratinocytes, in which matriptase was detected primarily at intercellular junctions, and prostasin primarily on membrane protrusion. Furthermore, upon induction of zymogen activation, free active prostasin remains cell-associated and free active matriptase is rapidly shed into the extracellular milieu. Our data suggest that matriptase and prostasin likely function as independent entities in human skin rather than as a tightly coupled proteolytic cascade as observed in mouse skin.

Highlights

The tightly coupled proteolytic cascade, composed of the type 2 transmembrane serine protease matriptase and the glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin, plays pivotal roles in the formation of the epidermal barrier in mouse skin (Leyvraz et al, 2005; List et al, 2002)
We investigate the functional relationship between human matriptase and prostasin by focusing on their tissue distribution profile in vivo in the human epidermis, hair follicles, and sebaceous gland, their subcellular localization and the fates of the active enzymes in vitro in HaCaT human keratinocytes
Our study reveals that in spite of the close functional link established with mouse models, human matriptase and human prostasin may function as independent entities and participate in different stages of differentiation in the three compartments of human skin

Summary

Introduction

The tightly coupled proteolytic cascade, composed of the type 2 transmembrane serine protease matriptase and the glycosylphosphatidylinositol (GPI)-anchored serine protease prostasin, plays pivotal roles in the formation of the epidermal barrier in mouse skin (Leyvraz et al, 2005; List et al, 2002). Genetic ablation of matriptase or prostasin causes severe impairment of epidermal barrier function leading to neonatal death for matriptase and prostasin knockout mice. Matriptase appears to function as an upstream activator for prostasin, converting the zymogen form into the active protease, since it has been shown that active prostasin is not detectable in the skin of matriptase knockout mice. Prostasin may be the only downstream protease responsible for mediating matriptase function in the formation of mouse epidermal barrier, given the almost identical epidermal defects observed in the skin of matriptase and prostasin knockout mice

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Results

Conclusion