Sign up for Table of Contents Alerts.

Email this page

Print this page

Report

Troy binding to lymphotoxin-α activates NFκB mediated transcription

Tsuyoshi Hashimoto, David Schlessinger and Chang-Yi Cui

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.

Troy is a TNFR superfamily member that is highly expressed in developing hair follicles. Its possible function and ligand in skin have, however, been unknown. Here we demonstrate that an immunomodulatory cytokine, lymphotoxin-α (LTα), is a functional ligand of Troy by 3 biochemical approaches: (1) Immunoprecipitation assays revealed that LTα, but not LTβ or any obligate combination of LTα and LTβ, binds to Troy. (2) Co-transfection of LTα with Troy sharply upregulated NFκB reporter transcription, whereas LTβ or a combination of LTα and LTβ did not. (3) Recombinant LTα protein upregulated NFκB activity through Troy in a dosedependent manner. We further found that LTα is expressed in dermal papillae of developing hair follicles, whereas Troy was expressed in adjacent matrix region. This suggested involvement of LTα-Troy signaling in mesenchyme-epithelium interactions during hair follicle development. However, in Troy mutant mice that we generated, hair subtype composition and morphology were altered slightly if at all. The present study thus suggested a subtle function of the newly identified LTα-Troy pathway in skin appendage development, however, it may have an additional action compensated by a parallel EDA signaling pathway.

Authors

Tsuyoshi Hashimoto

National Institute on Aging; Baltimore, MD

David Schlessinger

National Institute on Aging; Baltimore, MD

Chang-Yi Cui

National Institute on Aging; Baltimore, MD

This is an open-access article

 Download PDF

If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.