Transglutaminase-3 Enzyme: A Putative Actor in Human Hair Shaft Scaffolding?

Thibaut, S.; Cavusoglu, Nükhet; Becker, E. De; Zerbib, F.; Bednarczyk, Audrey; Schaeffer, Christine; Dorsselaer, Alain Van; Bernard, Bruno

doi:10.1038/jid.2008.231

Cited by 31 publications

(33 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…5D). We hypothesize that this early network is rather stabilized by isopeptide (γ-glutamyl-e-lysine) bonds between early KAPs and keratins, enabled by the previously established expression and activity of transglutaminase 3 at the base of the hair follicle (34).…”

Section: Discussionmentioning

confidence: 99%

Keratin network modifications lead to the mechanical stiffening of the hair follicle fiber

Bornschlögl

Bildstein

Thibaut

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

The complex mechanical properties of biomaterials such as hair, horn, skin, or bone are determined by the architecture of the underlying fibrous bionetworks. Although much is known about the influence of the cytoskeleton on the mechanics of isolated cells, this has been less studied in tridimensional tissues. We used the hair follicle as a model to link changes in the keratin network composition and architecture to the mechanical properties of the nascent hair. We show using atomic force microscopy that the soft keratinocyte matrix at the base of the follicle stiffens by a factor of ∼360, from 30 kPa to 11 MPa along the first millimeter of the follicle. The early mechanical stiffening is concomitant to an increase in diameter of the keratin macrofibrils, their continuous compaction, and increasingly parallel orientation. The related stiffening of the material follows a power law, typical of the mechanics of nonthermal bending-dominated fiber networks. In addition, we used X-ray diffraction to monitor changes in the (supra)molecular organization within the keratin fibers. At later keratinization stages, the inner mechanical properties of the macrofibrils dominate the stiffening due to the progressive setting up of the cystine network. Our findings corroborate existing models on the sequence of biological and structural events during hair keratinization.atomic force microscopy | elastic modulus | human hair follicle | biomechanics | X-ray diffraction B iological tissues are structurally complex materials with remarkable mechanics and elastic moduli that can range from a few pascals to several gigapascals (1-3). An active field aims at understanding how the local structural and mechanical properties of bionetworks define its macroscopic mechanics from a molecular scale toward a cellular and tissue scale (4-6). One challenge is that the properties of these networks have to be considered over multiple length and force scales with macroscopic mechanical forces being transduced from the whole tissue scale down to the cellular and molecular level and vice versa.At the cellular level, the last decades witnessed for a considerable advancement toward a better understanding of how the cytoskeleton composed of actin, microtubules, and intermediate filaments (IFs) determines cellular mechanics (1,(6)(7)(8). In vitro studies on isolated cells (6) and reconstituted in vitro bionetworks with controllable architecture and composition (9-12) considerably advanced our knowledge of cytoskeletal mechanics. However, these models are only approximations of the complex tridimensional architecture of most tissues. At the tissue level, the mechanical anisotropy together with the variety of mechanically different constituents usually hamper direct correlations between network architecture and mechanical properties (3, 13). Analytical models and computer modeling allow to theoretically link the macroscopic mechanical properties of the network with parameters of the local network architecture (5, 14, 15).The human hair follicle was used here...

show abstract

Section: Discussionmentioning

confidence: 99%

Keratin network modifications lead to the mechanical stiffening of the hair follicle fiber

Bornschlögl

Bildstein

Thibaut

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

View full text Add to dashboard Cite

show abstract

“…The CE is subsequently linked to the keratin intermediate filament network and, through the actions of TGase-1, to components of the lamellar lipid matrix. In hair follicles, TGase-3 probably functions to cross-link structural proteins of the hair fibre (24). …”

Section: Discussionmentioning

confidence: 99%

Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma

Stacey

Sulem

Guðbjartsson

et al. 2014

Human Molecular Genetics

View full text Add to dashboard Cite

To search for new sequence variants that confer risk of cutaneous basal cell carcinoma (BCC), we conducted a genome-wide association study of 38.5 million single nucleotide polymorphisms (SNPs) and small indels identified through whole-genome sequencing of 2230 Icelanders. We imputed genotypes for 4208 BCC patients and 109 408 controls using Illumina SNP chip typing data, carried out association tests and replicated the findings in independent population samples. We found new BCC susceptibility loci at TGM3 (rs214782[G], P = 5.5 × 10−17, OR = 1.29) and RGS22 (rs7006527[C], P = 8.7 × 10−13, OR = 0.77). TGM3 encodes transglutaminase type 3, which plays a key role in production of the cornified envelope during epidermal differentiation.

show abstract

“…Evaluation of normal human skin by others has demonstrated expression of TG3 in the upper epidermal layers, the stratum corneum, and hair follicles (15,16). No tissue-fixed TG3 Ag has been identified in the dermis.…”

Section: Discussionmentioning

confidence: 99%

Dermatitis Herpetiformis Sera or Goat Anti–Transglutaminase-3 Transferred to Human Skin-Grafted Mice Mimics Dermatitis Herpetiformis Immunopathology

Zone

Schmidt

Taylor

et al. 2011

The Journal of Immunology

View full text Add to dashboard Cite

Dermatitis herpetiformis (DH) is characterized by deposition of IgA in the papillary dermis. However, indirect immunofluorescence is routinely negative, raising the question of the mechanism of formation of these immune deposits. Sárdy et al. (2002. J. Exp. Med. 195: 747–757) reported that transglutaminase-3 (TG3) colocalizes with the IgA. We sought to create such deposits using passive transfer of Ab to SCID mice bearing human skin grafts. IgG fraction of goat anti-TG3 or control IgG were administered i.p. to 20 mice. Separately, sera from seven DH patients and seven controls were injected intradermally. Biopsies were removed and processed for routine histology as well as direct immunofluorescence. All mice that received goat anti-TG3 produced papillary dermal immune deposits, and these deposits reacted with both rabbit anti-TG3 and DH patient sera. Three DH sera high in IgA anti-TG3 also produced deposits of granular IgA and TG3. We hypothesize that the IgA class anti-TG3 Abs are directly responsible for the immune deposits and that the TG3 is from human epidermis, as this is its only source in our model. These deposits seem to form over weeks in a process similar to an Ouchterlony immunodiffusion precipitate. This process of deposition explains the negative indirect immunofluorescence results with DH serum.

show abstract

Transglutaminase-3 Enzyme: A Putative Actor in Human Hair Shaft Scaffolding?

Cited by 31 publications

References 54 publications

Keratin network modifications lead to the mechanical stiffening of the hair follicle fiber

Keratin network modifications lead to the mechanical stiffening of the hair follicle fiber

Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma

Dermatitis Herpetiformis Sera or Goat Anti–Transglutaminase-3 Transferred to Human Skin-Grafted Mice Mimics Dermatitis Herpetiformis Immunopathology

Contact Info

Product

Resources

About