Molecular Identification and Expression Analysis of Filaggrin-2, a Member of the S100 Fused-Type Protein Family
Open Access
- 22 April 2009
- journal article
- research article
- Published by Public Library of Science (PLoS) in PLOS ONE
- Vol. 4 (4), e5227
- https://doi.org/10.1371/journal.pone.0005227
Abstract
Genes of the S100 fused-type protein (SFTP) family are clustered within the epidermal differentiation complex and encode essential components that maintain epithelial homeostasis and barrier functions. Recent genetic studies have shown that mutations within the gene encoding the SFTP filaggrin cause ichthyosis vulgaris and are major predisposing factors for atopic dermatitis. As a vital component of healthy skin, filaggrin is also a precursor of natural moisturizing factors. Here we present the discovery of a member of this family, designated as filaggrin-2 (FLG2) that is expressed in human skin. The FLG2 gene encodes a histidine- and glutamine-rich protein of approximately 248 kDa, which shares common structural features with other SFTP members, in particular filaggrin. We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta. In cultured primary keratinocytes, FLG2 mRNA expression displayed almost the same kinetics as that of filaggrin following Ca2+ stimulation, suggesting an important role in molecular regulation of epidermal terminal differentiation. We provide evidences that like filaggrin, FLG2 is initially expressed by upper granular cells, proteolytically processed and deposited in the stratum granulosum and stratum corneum (SC) layers of normal epidermis. Thus, FLG2 and filaggrin may have overlapping and perhaps synergistic roles in the formation of the epidermal barrier, protecting the skin from environmental insults and the escape of moisture by offering precursors of natural moisturizing factors.Keywords
This publication has 71 references indexed in Scilit:
- When Skin Damage Causes DeathPLoS Biology, 2008
- Skin stem cells: rising to the surfaceThe Journal of cell biology, 2008
- The M-Coffee web server: a meta-method for computing multiple sequence alignments by combining alternative alignment methodsNucleic Acids Research, 2007
- Large-scale identification of human genes implicated in epidermal barrier functionGenome Biology, 2007
- Nature's answer to breaching the skin barrier: an innovative development for amputeesJournal of Anatomy, 2006
- Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitisNature Genetics, 2006
- The cornified envelope: a model of cell death in the skinNature Reviews Molecular Cell Biology, 2005
- BLAT—The BLAST-Like Alignment ToolGenome Research, 2002
- BLAST 2 Sequences, a new tool for comparing protein and nucleotide sequencesFEMS Microbiology Letters, 1999
- Gapped BLAST and PSI-BLAST: a new generation of protein database search programsNucleic Acids Research, 1997