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

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