The Role of Desmosomal and Corneodesmosomal Proteins on Skin and Hair Integrity - Term Paper Example

The Role of Desmosomal and Corneodesmosomal Proteins on Skin and Hair Integrity Name: Lecturer: Course: Date: Table of Contents Table of Contents 2 Overview 3 Preventing desquamation 4 Promotes skin elasticity 6 Ensure skin-barrier formation against diseases 7 Promotes turgidity and strength of stratum corneum 9 Prevents hair loss and aberrant skin differentiation 10 Concluding remarks 12 Overview Cellular junctions and corneodesmosomes derived from desmosomes and corneodesmosomes provide tough inter-corneocyte cohesion within the stratum corneum. Several proteins make up the major constituents of the extra-cellular section of the corneodesmosomes: desmocollin 1(DSC1), desmoglein 1 (DSG1), desmosomal cadherins, and corneodesmosin (CDSN), which is a glycoprotein derived from granular keratinocytes before being integrated into desmosomes (Caubet, 2004, p. 1235). A review of literature brings into perspective the role of desmosomal and corneodesmosomal proteins in ensuring corneocyte cohesion and indicated that the degradation of corneodesmosin within the corneocyte cohesion leads to desquamation (Jonca et al, 2010). On the other hand, clinical studies have observed that DSC1 accumulate within the stratum corneum of the epidermis, and that proteolysis of the DSCE is reduced within the corneum of dry skin. The cleavage of the DSGI has also been linked to desquamation and hyperkeratosis. Indeed, studies have indicated that degradation of corneodesmosomes is linked to the loss of the outer skin, through a process known as desquamation (Jonca 2010, 36; Sandjeu and Haftek 2009, 23). Additionally, the proteolytic cleavage found in the outer-cellular section of the cell-cell adhesive make-up has been found to be central to the process of desquamation (Caubet, 2004, p. 1235). Despite the copiousness of these studies, the molecules that cause cleavage of the corneodesmosomal proteins or their means of regulating are not fully understood. In this regards, this literature review explores the role of desmosomal and corneodesmosomal proteins on skin and hair integrity. Preventing desquamation By forestalling desquamation of the skin, the desmosomal and corneodesmosomal proteins promote skin integrity. According to Caubet (2004, p. 1235), Corneodesmosin is an adhesive protein found in the extra-cellular section of the corneodesmosomes, which are the intersectional structure that arbitrate corneocyte cohesion. Caubet (2004, p. 1235) found that when these proteins degrade at the surface of the epidermis, desquamation occurs. In essence, this evokes the role of these proteins in promoting the integrity of the skin by preventing desquamation or exfoliation. However, the role is subject to their functional conditions and capabilities. This is since the occurrence of degradation leaves the skin susceptible to desquamation. To explore this hypothesis, Caubet et al. (2004, 1235) analysed the capacity of two enzymes: stratum corneum tryptic enzyme (SCTE) and the stratum corneum chymotryptic enzyme (SCCE) and to cleave desmocollin 1, desmoglein 1, as well as the epidermal forms of the corneodesmosin at an acidic pH that almost equalled that of the stratum corneum. The researchers found that while SCCE managed to cleave Corneodesmosin and desmocollin 1, it was not able to degrade desmoglein 1. However, the three corneodesmosomal proteins degraded once they were incubated with SCTE, leading to desquamation. The results indicate that while the corneodesmosomal proteins protected the skin before they were degraded, their degradation exposes the skin to desquamation (Caubet et al. 2004, 1235). Jonca (2010, p.37) provided similar analysis in his recent study of the functions and structure of Corneodesmosin and its contribution to pathophysiology. Jonca (2010, p.36) was categorical that the Corneodesmosin’s striking feature is its potential to contain high glycerine and serine content. In regards to the ends of the keratins, the glycerine- and serine-rich fields form the structures known as the glycine loops, which are the outcome of the connection to the interspersed aliphatic residues. As stated by Jonca’s (2010, 37-38), the capability of the glycine loop domains to mediate intermolecular adhesion has been investigated and confirmed in a later study by Darlenski et al. (2011, 36). Consistent with the previous research, Jonca (2010, 37-38) found that these kind of molecular interactions promote skin homeostasis as mutations within Keratin’s glycine loops result to occurrence of human cutaneous diseases such as palmoplantar keratodermas. Jonca’s (2010, 37-38) investigated the function of Corneodesmosin in the cellular interactions using mouse L-fibroblasts, which represented the chimeric protein made up of the human Corneodesmosin. In this respect, it could be argued that when the Corneodesmosin is based on the cell surface, it arbitrates cellular aggregation. Consistent with these findings was also another study by Caubet (2004, 122) who conducted quantitative analysis using surface-plasmon resonance and bacterial recombinant forms of corneodesmosin that confirmed the homophilic adhesive features of proteins. Overall, maintaining the integrity of the skin ensures that the body's homeostasis is upheld. The barrier functionality of the skin substantially depends on the end product of epidermal cell differentiation, such as stratum corneum. Since the epidermis intermittently self-renews, the likely desquamation is sufficiently balanced off through proliferation within the skin's basal layer. On the other hand, cohesion within the epidermis is contingent on the occurrence of corneodesmosin and specialised adhesive junctions (Sandjeu and Haftek, 2009, p.23) Promotes skin elasticity Corneodesmosomal proteins promote skin elasticity. To ensure this, Corneodesmosomal proteins provide the junction elasticity that prevents breaking of the intermolecular cells, immediately the cell envelope regains its rigidity. However, it is difficult to establish from the survey of literature whether the underlying molecular mechanism, through which desmosomal and corneodesmosomal proteins assumed an adhesive quality function while inside the corneodesmosome is yet to be fully explored. Some attempts to elucidate the process were made by Caubet et al. (2004, 747-752), who discussed that corneodesmosin gene toughness cohesion through its own adhesive qualities. In contrast, adhesion ensured by the glycine-loop domains has largely been evoked in elucidating their roles in mediating constantly adaptable and reversible intermolecular links. While Jonca (2010, 37) offer direction into the concept of skin elasticity, they do not provide an explanation on the mechanism of skin hydration and elasticity in respect to the desmosomal and corneodesmosomal proteins. Such an analysis calls to attention the concept of skin elasticity as interpreted by other authors. In fact, some researchers have focused their studies on determining in the area (Sandra et al. 2011, 363). For instance, Jae-We (2011, 225-229) explored the concept and established that while clinical evidences such as anti-inflammatory effects, skin hydration and skin elasticity have been proven in clinical trials, a clear-cut mechanism of skin hydration and elasticity have not been fully explored. In the research, Jae-We (2011, 225-229) centred on the skin hydration mechanism linked to matrix metalloproteinase (MMP), collagen, and flaggrin in animal and in vitro studies. Jae-We (2011, 225-229) concluded that skin hydration mechanism is a result of the recovery of filaggrin, increase generation of collagen and restraint of MMP. Either way, a large body of literature that examined adhesion resulting from glycine-loop domains arrived at a consensus that glycine-loop domains mediated adaptable and reversible intermolecular adjustment, which ensures skin elasticity. Consistent with the discussion, desmosomal and corneodesmosomal proteins could provide the junction elasticity to avert breaking immediately cell envelope regains its rigidity. Ensure skin-barrier formation against diseases The desmosomal and corneodesmosomal proteins ensure skin-barrier formation. They also preserve the barriers through maintenance of the integrity of the demosome (Orru et al. 2005, 164). Taking this assumption into perspective, Darlenski et al. (2011, 36) posited that protecting the integrity of the demosome in turn ensures that the integrity of the skin and hair is sustained. Review of literature on engineered mouse models and human diseases evidences the significance of desmosomal and corneodesmosomal proteins in protecting the skin and hair from diseases such as hypotrichosis, which is a rare disease of the scalp that results in baldness in children (Leclerc 2009, 2699; Sandjeu and Haftek 2009, 23-30). As stated by Bhushan et al. (2009 4401-03), the corneodesmosomal proteins within the intercellular junctions offer tough cohesion between the adjacent cells. Despite this, Sandjeu and Haftek (2009, 23-30) offered a conflicting perspective by asserting that mutation of the genes that encode the desmosal components are habitually responsible for skin ailments linked to heart defects. To give credence to the validity of his statement, Leclerc (2009, 2699) investigated in vitro corneodesmosin gene mutation and how it triggers desmosome dysfunction, which in turn leads to hair-follicle degeneration and lethal skinbarrier in mice. Leclerc (2009, 2699) conducted structural analysis and found that desmosomal dysfunction at the crossing point between the cornified and the living layers. In the study, Leclerc’s (2009, 2699) established chronic defect in epidermal permeability barrier. Hence, it could be argued that desmosomal and corneodesmosomal proteins barriers ensure skin-barrier formation, which is essential throughout life in preserving the barriers by maintaining the integrity of the desmosome. By sustaining the integrity of the desmosome, the skin and hair subsequently becomes sustained. Jonca’s et al. (2010, 36) review of literature corroborated these findings. Hence, while the corneodesmosomal proteins serve to protect the integrity of the skin, their mutation leaves the skin vulnerable to skin ailments. Consistent with Leclerc’s (2009, p.2699) analysis, Sandjeu and Haftek (2009, 23-30) concluded that mutation of corneodesmosin is linked to hypotrichosis. In a study of the role of kallikrein serine proteases in epidermal desquamation, Borgono et al. (2009, p3640) also established a link between corneodesmosomal proteins and desquamation. Results indicated that the corneodesmosomes keep tissue integrity, as well as mediate the adhesion of the cells between the desmosomal cadherins. According to Jonca 2011 (1381), the critical role of the desmosomal and corneodesmosomal proteins is confirmed in the mouse, since inactivation of its gene is lethal few hours after birth. On the other hand, nonsense corneodesmosin mutation has been indicated to be responsible for hypotrichosis. Promotes turgidity and strength of stratum corneum The desmosomal and corneodesmosomal proteins promote the turgidity and strength of stratum corneum’s structural components. A study by Kim et al. (2011, p.439) observed that while corneodesmosomes are significant structures for adhesion that ensure the solidity of epidermal, retinoids have been suspected to affect corneodesmosomes. To examine such inconsistencies, Kim et al. (2011, p.439) examined how retinoid can affect the outcome of corneodesmosomal constituents such as kallikrein (KLK), desmocollin (DSC), and corneodesmosin (CDSN). Kim et al. (2011, 439) applied ethanol on the back of a hairless mice, so as to examine the structural components of stratum corneum, using an electronic microscope. Results indicated that retinol boosted the detachment of corneocyte, as well as corneodesmosomes degradation. Commenting on the results, Kim et al. (2011, p.439) stated that the down-regulation of desmocollin and desmoglein by the all-trans-retinoic acid (RA) indicated the increase in the degradation of corneodesmosomes and subsequently the retinoids. From these results, it could be argued that while retinoids affect the functioning of corneodesmosomals, the latter affects the turgidity and strength of stratum corneum’s structural components. Descargues (2011, p.1622–1632) investigated why corneodesmosomal cadherins are stratum corneum trypsin’s preferred targets using light microscopy. The research investigated 15 Netherton syndrome (NS) patients. The patients originated from North Africa (mainly Mali and Morocco) and Europe (mainly Kosovo, Italy and France). Descargues et al. (2011, 1622–1632) based their analysis on the patients’ family history and results of clinical examination. The parameters of the study included the defects of the hair shaft (trichorrhexis invaginata), and ichthyosis linearis circumflexa. Descargues (2011, p.1622–1632) found that the 15 patients indicated several abnormalities when compared to the normal epidermis. Additionally, cases of acanthosis linked to papillomatosis were noted. The results indicated that 11 of the 15 patients exhibited thickening of the stratum corneum. On the other hand, cases of diminished granular layer in NS epidermis were observed. Descargues (2011, 1622–1632) also observed distinct hypergranulosis in 9 of patients examined. The studies collated from investigations of corneodesmosomes using mouse models and study of human diseases leads to the understanding of the primordial functions of desmosomal and corneodesmosomal proteins in ensuring turgidity and strength of stratum corneum (Jonca et al. 2004). Despite this polemic understanding, certain functional dimensions relating to corneodesmosomes have not been implicitly understood, particularly at the molecular level. This conception is indeed supported by immunoelectron microscopy experiments, which showed that desmosomal and corneodesmosomal proteins tend to wholly localise to the extra-cellular centre of corneodesmosomes in the stratum corneum. Several researchers have offered their view on how the localisation is achieved by alluding to the fact that a pre-existing element of the extra-cellular section of the junctions interrelates with the corneodesmosomes (Jonca et al. 2011). Despite his conception, it is critical to argue that studies have failed to prove any interrelation between the desmosomal cadherins and corneodesmosomal proteins. Indeed, from a survey of literature, it is clear that research literature has not explored such interaction and that the molecular partners of desmosomal proteins are yet to be identified. Prevents hair loss and aberrant skin differentiation While there exists momentous debate on the role of desmosomal and corneodesmosomal to promote skin and hair integrity, genetic studies suggest that the corneodesmosin gene mutation in the psoriasis-susceptibility locus is linked to the risks of psoriasis (Caubet et al. 2010, 3416). Mitsuru (2008, 6720-6724) defines psoriasis as a skin condition that features growth and abnormal differentiation of keratinocytes. The corneodesmosin is also found in the inner root of hair follicle and that nonsense mutation of psoriasis gene is leads to the scalp specific hair loss. Mitsuru (2008, 6720-6724) studied the pathogenetic role of corneodesmosin dysfunction in causing skin disease by using a mouse strain. His results showed that corneodesmosin gene mutation contributes to psoriasis susceptibility. The findings link corneodesmosomes to an inflammatory disease, including psoriasis. Jonca (2010, p.37) conducted document analysis to determine the functions of corneodesmosomes and established grounds to suggest that corneodesmosomes is of critical interest when it comes to analysis of psoriasis. Indeed, this argument is reinforced by the conception that corneodesmosomes is localised to chromosome 6p21 at PSORS1, which is the central vulnerability locus of psoriaris. In his review of published literature, Jonca (2011, 1381) concluded that corneodesmosomes is highly polymorphic and could lead to psoriasis. Different studies have also examined the role of desmosomal and corneodesmosomal proteins in preventing skin disorders. In a landmark study by Jonca (2010, 37), it was revealed that a common feature of some skin disorders is scaling, which is often linked to the thickening of the stratum corneum. In their document analysis of published literature to establish the function and structure of corneodesmosal, Jonca (2010, 37), discussed that hyperkeratosis may be caused by intensified cell proliferation or desquamation. Some researchers such as Sevilla (2007, 1599-1612) have linked hyperkeratosis to the occurrence of peripheral corneodesmosomes at the outer layer of the stratum corneum, a property related to the normal palmoplantar epidermis. Sevilla’s (2007, p.1599-1612) conceptualisation of the link between hyperkeratosis and the occurrence of peripheral corneodesmosomes is corroborated by Jonca (2010, p.37). In his review of literature, Jonca (2010, p.37) mentioned that the link has been accurately documented in cases of winter xerosis and congenital ichthyoses. Separately, it could be argued that the increased levels of corneodesmosomes are detected in some inflammatory diseases, including hyperkeratotic lesions (Jonca, 2010, p.37). In discussing the link between hyperkeratosis and the occurrence of peripheral corneodesmosomes, Jonca (2010, p.37) pointed to findings that suggested that mutations in some genes are identifiable as responsible for causing ichtyosis although none of them has been related to mutations in corneodesmosomes. Concluding remarks The desmosomal and corneodesmosomal proteins barriers ensure skin-barrier formation, which is essential throughout life in preserving the skin-barriers by maintaining the integrity of the desmosome. By sustaining the integrity of the desmosome, the skin and hair subsequently becomes sustained. This implies that maintaining the integrity of the skin in return ensures that the body's homeostasis is upheld. However, when the desmosomal and corneodesmosomal proteins degrade at the surface of the epidermis, desquamation occurs. However, the role is subject to their conditions and capabilities. This is since the occurrence of degradation leaves the skin susceptible to desquamation. Review of literature on engineered mouse models and human diseases argues the role of of desmosomal and corneodesmosomal proteins in protecting the skin and hair from diseases such as hypotrichosis. By forestalling desquamation of the skin, these proteins promote skin integrity, ensure skin-barrier formation as well as preserve the skin barriers through maintenance of the integrity of the desmosome. In return, by sustaining the integrity of the desmosome, that of the skin and hair also becomes sustained. Corneodesmosomal proteins also promote skin elasticity. To ensure this, these proteins provide the junction elasticity that prevents breaking of the intermolecular cells immediately the cell envelope regains its rigidity. However, it is difficult to establish from the survey of literature whether the underlying molecular mechanism through which desmosomal and corneodesmosomal proteins assumed an adhesive quality function while inside the corneodesmosome. Reference List Desai, Bhushan, Robert Harmon and Kathleen Green. 2009. “Desmosomes at a glance”. Journal of Cell Science 122(1): 4401-4407 Borgono, Carla, Iacovos Michael, Nahoko Komatsu, Arumugam Jayakumar and Ravi Kapadia et al. 2009. “A Potential Role for Multiple Tissue Kallikrein Serine Proteases in Epidermal Desquamation.” The Journal Of Biological Chemistry 282(6): 3640 –3652 Caubet, Cecil, Nathalie Jonca, Maria Brattsand, Marina Guerrin, Dominique Bernard and Rainer Schmidt. 2004. "Degradation of Corneodesmosome Proteins by Two Serine Proteases of the Kallikrein Family, SCTE/KLK5/hK5 and SCCE/KLK7/hK7." Journal Invest Dermatol 122:1235 –1244 Caubet, Ce´cile, Luc Bousset, Ole Clemmensen, Yannick Sourigues, Anette Bygum et al. 2010. "A new amyloidosis caused by fibrillar aggregates of mutated corneodesmosin." The FASEB Journal 24(1): 3416-34-24 Darlenski, R. J. Kazandjieva and N. Tsankov. 2011."Skin Barrier Function: Morphological Basis And Regulatory Mechanisms." Journal Clin Med. 4(1):36-45 Descargues, Pacal, Céline Deraison, Catherine Prost, Sylvie Fraitag and Juliette Mazereeuw-Hautier et al. 2006. “Corneodesmosomal Cadherins Are Preferential Targets of Stratum Corneum Trypsin- and Chymotrypsin-like Hyperactivity in Netherton Syndrome. Journal of Investigative Dermatology 126: 1622–1632. Jae-We, Cho, Yeon-su Jeong, and Soo-Muk Cho. 2011. "Skin Hydration and Collagen Synthesis of AF-343 in HS68 Cell Line and NC/Nga Mice by Filaggrin Expression and Suppression of Matrix Metallopreteinase." Toxicology Research 27(1): 225-229 Jonca, Nathalie, Cécile Caubet, Marina Guerrin, Michel Simon and Guy Serre. 2010. "Corneodesmosin: Structure, Function and Involvement in Pathophysiology." The Open Dermatology Journal, 4: 36-45 Jonca, Nathalie, écile Caubet, Emilie A Leclerc1, Marina Guerrin1, Michel Simon1 and Guy Serre. 2011. "Protease Sensitivity of Corneodesmosin Variants Encoded by the Six More Common CDSN Haplotypes." Journal of Investigative Dermatology 131(1):1381–1384 Kim, Moon, Sang Eun Lee, Jae Yong Chang, & Soo-Chan Kim. 2011. Retinoid Induces the Degradation of Corneodesmosomes and Downregulation of Corneodesmosomal Cadherins: Implications on the Mechanism of Retinoid-induced Desquamation." Ann Dermatol 23(4): 239-447 Leclerc, Emilie, Anne Huchenq1, Nicolas Mattiuzzo1, Daniel Metzger and Pierre Chambon. 2009. "Corneodesmosin gene ablation induces lethal skinbarrier disruption and hair-follicle degeneration related to desmosome dysfunction." Journal of Cell Science 122: 2699-2709 Mitsuru Matsumoto, Yiqing Zhou, and David D. Chaplin. 2008. Targeted deletion of the murine corneodesmosin gene delineates its essential role in skin and hair physiology. Proc Natl Sci 105(18): 6720-6724 Orru, Sandro, Erika Giuressi, Carlo Carcassi, Mirella Casula and Licinio Contu. "Mapping of the Major Psoriasis-Susceptibility Locus (PSORS1) in a 70-Kb Interval around the Corneodesmosin Gene (CDSN)." Am. J. Hum. Genet. 76 (2005):164–171 Sandra, Maruyama1, Elen Anatriello1, Jennifer Anderson and José Ribeiro et al. 2011. The expression of genes coding for distinct types of glycine-rich proteins varies according to the biology of three metastriate ticks, Rhipicephalus (Boophilus) microplus, Rhipicephalus sanguineus and Amblyomma cajennense. BMC Genomics11:363 Sandjeu, Y. and Haftek, M. 2009. "Desmosealin And Other Components Of The Epidermal Extracellular Matrix.” Journal of Physiology And Pharmacology 60(4): 23-30 Sevilla, Lisa, Rachida Nachat and Fiona M. Watt. 2007. "Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier." Journal of Cellular Biology 179(7): 1599-1612 Read More