Format

Send to

Choose Destination
J Invest Dermatol. 2017 Feb;137(2):422-429. doi: 10.1016/j.jid.2016.09.030. Epub 2016 Oct 11.

Deimination of Human Hornerin Enhances its Processing by Calpain-1 and its Cross-Linking by Transglutaminases.

Author information

1
Unité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université de Toulouse Midi-Pyrénées, Université Toulouse III, Toulouse, France.
2
Institut de Pharmacologie et de Biologie Structurale, Université de Toulouse Midi-Pyrénées, CNRS, Université Toulouse III, Toulouse, France.
3
School of Agriculture, University of Ibaraki, Ibaraki, Japan.
4
Unité Différenciation Epithéliale et Autoimmunité Rhumatoïde, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), Université de Toulouse Midi-Pyrénées, Université Toulouse III, Toulouse, France. Electronic address: michel.simon@inserm.fr.

Abstract

Hornerin (HRNR) shares numerous features with filaggrin, a key contributor to the epidermal barrier functions. The two proteins display a related structural organization, are expressed by the granular keratinocytes as a large precursor processed by proteolysis, and are cross-linked to the cornified cell envelopes. Two main steps in the metabolism of filaggrin are its deimination and calpain-1 cleavage. Here, using ion-exchange chromatography and two-dimensional gel electrophoresis of human epidermis extracts, we determined that HRNR is deiminated in vivo. Accordingly, cornified envelopes, purified from plantar and abdominal human skin, were shown to contain deiminated proteins. A recombinant form of HRNR (HRNRHis) deiminated in vitro was shown to be a better substrate for transglutaminases 1 and 3 than the unmodified form. Our data also indicated that calpain-1 may be involved in the proteolytic processing of HRNR, because calpain-1 was co-located with HRNR in the cytoplasm of granular keratinocytes. Using Western blotting and mass spectrometry analysis, HRNRHis was shown to be cleaved by calpain-1 in vitro, its deimination enhancing its proteolysis. In HRNR full sequence, four calpain-1 cleavage sites were identified. Altogether, these data allowed a new role to be deciphered for deimination during cornification and provided further characterization of HRNR metabolism.

PMID:
27742573
DOI:
10.1016/j.jid.2016.09.030
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center