Dynamic Interactions of Epidermal Collagen XVII with the Extracellular Matrix

Nishie, Wataru; Kiritsi, Dimitra; Nyström, Alexander; Hofmann, Silke; Bruckner‐Tuderman, Leena

doi:10.1016/j.ajpath.2011.04.019

Cited by 68 publications

(72 citation statements)

References 34 publications

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“…Consistent with this notion, we have shown that migrating keratinocytes constitutively shed and leave the collagenous ectodomain of collagen XVII in the extracellular matrix (22,23). However, the regulation mechanisms of collagen XVII ectodomain shedding are still unclear.…”

supporting

confidence: 65%

“…For detection of the intracytoplasmic domain of collagen XVII, the polyclonal goat antibody N18 (Santa Cruz Biotechnology) was diluted 1:500. A new rabbit polyclonal antibody (Ab-SILP) was produced using the synthetic peptide NH 2 -SILPYGDS, as described previously (16,23). Purification of the Ab-SILP was performed using SulfoLink coupling resin (20404, Thermo Scientific) according to the manufacturer's instructions, and the final concentration of 1 g/ml of the antibody was used.…”

Section: In Silico Prediction and Targeting Potential Coiled Coils Onmentioning

confidence: 99%

“…To establish stably expressing cell lines, pcDNA5/FRT plasmid with wild type and mutant collagen XVII cDNA, as well as the empty vector as a control, were co-transfected with pOG44 into the Flp-In-293 host cells by Lipofectamine 2000 (Invitrogen). Stably expressing cells were selected under 200 g/ml hygromycin B (Invitrogen), as described previously (16,23).…”

Section: In Silico Prediction and Targeting Potential Coiled Coils Onmentioning

confidence: 99%

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Coiled Coils Ensure the Physiological Ectodomain Shedding of Collagen XVII

Nishie

Jacków

Hofmann

et al. 2012

Journal of Biological Chemistry

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Background: ␣-Helical coiled coils represent potential oligomerization motifs in vital proteins. Results: Targeting coiled coils in the juxtamembranous linker region of transmembrane collagen XVII significantly increased intracellular cleavage by unmasking a furin recognition sequence. Conclusion: Coiled coils in collagen XVII play a pivotal role to ensure its physiological ectodomain shedding. Significance: This study revealed a novel role of coiled coils as stabilizer of a specific protease cleavage site.

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supporting

confidence: 65%

Section: In Silico Prediction and Targeting Potential Coiled Coils Onmentioning

confidence: 99%

Section: In Silico Prediction and Targeting Potential Coiled Coils Onmentioning

confidence: 99%

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Coiled Coils Ensure the Physiological Ectodomain Shedding of Collagen XVII

Nishie

Jacków

Hofmann

et al. 2012

Journal of Biological Chemistry

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“…However, more detailed analysis is required to clarify the exact role of collagen XVII during glomerular development. At the dermal-epidermal junction, the main intracellular binding partners of collagen XVII are BP230, plectin and integrin β4 subunit, whereas the extracellular part of collagen XVII interacts with laminin-332 (α3β3γ2) and the integrin α6 subunit (Van den Bergh and Giudice 2003; Aumailley et al 2006;Mihai and Sitaru 2007;Nishie et al 2011). In mature kidney, the major integrin complex, α3β1, is located in the FPs of podocytes at the interface with GBM, Bowman's capsule, mesangial cells and the basal aspect of distal tubular cells (Adler 1992;Patrakka and Tryggvason 2010).…”

Section: Discussionmentioning

confidence: 99%

Transmembrane collagen XVII is a novel component of the glomerular filtration barrier

et al. 2012

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The kidney filtration barrier consists of the capillary endothelium, the glomerular basement membrane and the slit diaphragm localized between foot processes of neighbouring podocytes. We report that collagen XVII, a transmembrane molecule known to be required for epithelial adhesion, is expressed in podocytes of normal human and mouse kidneys and in endothelial cells of the glomerular filtration barrier. Immunoelectron microscopy has revealed that collagen XVII is localized in foot processes of podocytes and in the glomerular basement membrane. Its role in kidney has been analysed in knockout mice, which survive to birth but have high neonatal mortality and skin blistering and structural abnormalities in their glomeruli. Morphometric analysis has shown increases in glomerular volume fraction and surface densities of knockout kidneys, indicating an increased glomerular amount in the cortex. Collagen XVII deficiency causes effacement of podocyte foot processes; however, major slit diaphragm disruptions have not been detected. The glomerular basement membrane is split in areas in which glomerular and endothelial basement membranes meet. Differences in the expression of collagen IV, integrins α3 or β1, laminin α5 and nephrin have not been observed in mutant mice compared with controls. We propose that collagen XVII has a function in the attachment of podocyte foot processes to the glomerular basement membrane. It probably contributes to podocyte maturation and might have a role in glomerular filtration.

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“…Hemidesmosomes are multimolecular complexes that promote the stable adhesion of epithelial cells to the underlying extracellular matrix. COL17 is known to interact with BP230, plectin, a 6 b 4 integrin, laminin 332, and collagen IV (51)(52)(53). There is a possibility that COL17-humanized mice have less skin stability than do wild-type mice owing to the insufficient interaction between hCOL17 and other murine components, which may lead to skin fragility in COL17-humanized mice in a complement-independent manner, although we have shown that without the transfer of pathogenic Abs, neonatal COL17-humanized mice skin is intact (Tables I-IV).…”

Section: Discussionmentioning

confidence: 99%

Bullous Pemphigoid Autoantibodies Directly Induce Blister Formation without Complement Activation

Ujiie

Sasaoka

Izumi

et al. 2014

The Journal of Immunology

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Complement activation and subsequent recruitment of inflammatory cells at the dermal/epidermal junction are thought to be essential for blister formation in bullous pemphigoid (BP), an autoimmune blistering disease induced by autoantibodies against type XVII collagen (COL17); however, this theory does not fully explain the pathological features of BP. Recently, the involvement of complement-independent pathways has been proposed. To directly address the question of the necessity of the complement activation in blister formation, we generated C3-deficient COL17-humanized mice. First, we show that passive transfer of autoantibodies from BP patients induced blister formation in neonatal C3-deficient COL17-humanized mice without complement activation. By using newly generated human and murine mAbs against the pathogenic noncollagenous 16A domain of COL17 with high (human IgG1, murine IgG2), low (murine IgG1), or no (human IgG4) complement activation abilities, we demonstrate that the deposition of Abs, and not complements, is relevant to the induction of blister formation in neonatal and adult mice. Notably, passive transfer of BP autoantibodies reduced the amount of COL17 in lesional mice skin, as observed in cultured normal human keratinocytes treated with the same Abs. Moreover, the COL17 depletion was associated with a ubiquitin/proteasome pathway. In conclusion, the COL17 depletion induced by BP autoantibodies, and not complement activation, is essential for the blister formation under our experimental system.

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Dynamic Interactions of Epidermal Collagen XVII with the Extracellular Matrix

Abstract: The extracellular matrix (ECM) is not merely a supporting scaffold for tissue and organ architecture. The ECM can bind and release growth factors, which regulate many biologic processes and cell functions, including migration, differentiation, and proliferation.

Cited by 68 publications

References 34 publications

Coiled Coils Ensure the Physiological Ectodomain Shedding of Collagen XVII

Coiled Coils Ensure the Physiological Ectodomain Shedding of Collagen XVII

Transmembrane collagen XVII is a novel component of the glomerular filtration barrier

Bullous Pemphigoid Autoantibodies Directly Induce Blister Formation without Complement Activation

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