Limits...
Molecular identification and expression analysis of filaggrin-2, a member of the S100 fused-type protein family.

Wu Z, Hansmann B, Meyer-Hoffert U, Gläser R, Schröder JM - PLoS ONE (2009)

Bottom Line: We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.

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 Ca(2+) 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.

Show MeSH

Related in: MedlinePlus

Unrooted tree of filaggrin-2 repeat domains together with typical domains of hornerin and profilaggrin.This neighbour-joining cladogram tree [68], depicting relationships among A- and B-type repeats, is constructed based on the alignment. The bootstrap consensus tree is inferred from 1000 replicates [69]. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. All positions containing gaps and missing data were eliminated from the dataset (complete deletion option). There were a total of 71 positions in the final dataset. Phylogenetic analyses were conducted in MEGA4 [66]. Numbers in nodes correspond to bootstrap support values indicated as percentages.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2668185&req=5

pone-0005227-g003: Unrooted tree of filaggrin-2 repeat domains together with typical domains of hornerin and profilaggrin.This neighbour-joining cladogram tree [68], depicting relationships among A- and B-type repeats, is constructed based on the alignment. The bootstrap consensus tree is inferred from 1000 replicates [69]. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. All positions containing gaps and missing data were eliminated from the dataset (complete deletion option). There were a total of 71 positions in the final dataset. Phylogenetic analyses were conducted in MEGA4 [66]. Numbers in nodes correspond to bootstrap support values indicated as percentages.

Mentions: In particular, the filaggrin-2 protein is characterized by two arrays of ordered repetitive structures separated by a spacer sequence (residues 1154–1222) (Fig. 2A). The A-type repetitive domain region is located between residues 467 and 1153, the middle part of filaggrin-2. It is comprised of nine conserved repeats, each having a size of 75∼77 amino acids (A1 to A9) characterized with four regularly spaced phenylalanine residues twelve amino acids apart (Fig. 2C). The B-type repetitive domain region is located between residues 1246 and 2303 and just in front of the C-terminal 88-residue domain. It is comprised of fourteen conserved repeats of 75∼77 amino acids (B1 to B14), but these repeats do not have any regularly spaced phenylalanine (Fig. 2D). By using these tandem repeats as queries in BLAST homolog searches against the human protein database, the most positive hit homologous to each A-type repeat was from repetitive domains of hornerin (50–77% identity) whereas that homologous to each B-type repeat was from filaggrin units (28–39% identity) (data not shown). Multiple alignments of these repeat domains together with one representative peptide of their corresponding homolog, respectively, further addressed their homology relationships (Fig. 2C and D). In addition, a neighbour-joining tree was constructed based on alignment of all FLG2 repeats together with their representative homologous repeat units of filaggrin and hornerin, demonstrating different evolutionary histories for the A-type and B-type repeats (Fig. 3).


Molecular identification and expression analysis of filaggrin-2, a member of the S100 fused-type protein family.

Wu Z, Hansmann B, Meyer-Hoffert U, Gläser R, Schröder JM - PLoS ONE (2009)

Unrooted tree of filaggrin-2 repeat domains together with typical domains of hornerin and profilaggrin.This neighbour-joining cladogram tree [68], depicting relationships among A- and B-type repeats, is constructed based on the alignment. The bootstrap consensus tree is inferred from 1000 replicates [69]. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. All positions containing gaps and missing data were eliminated from the dataset (complete deletion option). There were a total of 71 positions in the final dataset. Phylogenetic analyses were conducted in MEGA4 [66]. Numbers in nodes correspond to bootstrap support values indicated as percentages.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2668185&req=5

pone-0005227-g003: Unrooted tree of filaggrin-2 repeat domains together with typical domains of hornerin and profilaggrin.This neighbour-joining cladogram tree [68], depicting relationships among A- and B-type repeats, is constructed based on the alignment. The bootstrap consensus tree is inferred from 1000 replicates [69]. Branches corresponding to partitions reproduced in less than 50% bootstrap replicates are collapsed. The tree is drawn to scale, with branch lengths in the same units as those of the evolutionary distances used to infer the phylogenetic tree. All positions containing gaps and missing data were eliminated from the dataset (complete deletion option). There were a total of 71 positions in the final dataset. Phylogenetic analyses were conducted in MEGA4 [66]. Numbers in nodes correspond to bootstrap support values indicated as percentages.
Mentions: In particular, the filaggrin-2 protein is characterized by two arrays of ordered repetitive structures separated by a spacer sequence (residues 1154–1222) (Fig. 2A). The A-type repetitive domain region is located between residues 467 and 1153, the middle part of filaggrin-2. It is comprised of nine conserved repeats, each having a size of 75∼77 amino acids (A1 to A9) characterized with four regularly spaced phenylalanine residues twelve amino acids apart (Fig. 2C). The B-type repetitive domain region is located between residues 1246 and 2303 and just in front of the C-terminal 88-residue domain. It is comprised of fourteen conserved repeats of 75∼77 amino acids (B1 to B14), but these repeats do not have any regularly spaced phenylalanine (Fig. 2D). By using these tandem repeats as queries in BLAST homolog searches against the human protein database, the most positive hit homologous to each A-type repeat was from repetitive domains of hornerin (50–77% identity) whereas that homologous to each B-type repeat was from filaggrin units (28–39% identity) (data not shown). Multiple alignments of these repeat domains together with one representative peptide of their corresponding homolog, respectively, further addressed their homology relationships (Fig. 2C and D). In addition, a neighbour-joining tree was constructed based on alignment of all FLG2 repeats together with their representative homologous repeat units of filaggrin and hornerin, demonstrating different evolutionary histories for the A-type and B-type repeats (Fig. 3).

Bottom Line: We found that FLG2 transcripts are present in skin, thymus, tonsils, stomach, testis and placenta.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Dermatology, University Hospital of Schleswig-Holstein, Kiel, Germany.

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 Ca(2+) 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.

Show MeSH
Related in: MedlinePlus