Collagen XVII Shedding Suppresses Re-Epithelialization by Directing Keratinocyte Migration and Dampening mTOR Signaling

The Journal of Investigative Dermatology
Joanna JackówClaus-Werner Franzke

Abstract

Transmembrane collagen XVII is traditionally viewed as an important hemidesmosomal attachment component that promotes stable dermal-epidermal adhesion in the skin. However, its expression is highly elevated at the leading edges of cutaneous wounds or invasive carcinomas, suggesting alternative functions in cell migration. The collagenous ectodomain of collagen XVII is constitutively shed from the cell surface by a disintegrin and metalloproteinases, and this shedding is strongly induced during wound healing. Recently, we investigated the physiological relevance of collagen XVII shedding by generating knock-in mice, which exclusively express a functional non-sheddable collagen XVII mutant. Prevention of ectodomain shedding in these mice caused no spontaneous phenotype in resting skin, but accelerated re-epithelialization on skin wounding. Here, we investigated the mechanistic function of shedding during wound healing. Using the non-shedding collagen XVII mice as a model, we uncovered ectodomain shedding as a highly dynamic modulator of in vivo proliferation and motility of activated keratinocytes through tight coordination of α6β4 integrin-laminin-332 interactions and dampening of mechanistic target of rapamycin signaling at the...Continue Reading

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Citations

Nov 18, 2016·International Journal of Molecular Sciences·Stefanie LöffekIris Helfrich
Mar 30, 2017·The Journal of Investigative Dermatology·Yale LiuYumin Xia
Dec 26, 2017·Frontiers in Immunology·Yale LiuYumin Xia
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Jun 20, 2020·Expert Review of Proteomics·Jörn DengjelAlexander Nyström
Sep 2, 2020·European Journal of Oral Sciences·Olav SchreursKarl Schenck
Sep 2, 2020·Experimental Dermatology·Alexander Nyström, Dimitra Kiritsi
Jul 17, 2020·Frontiers in Cell and Developmental Biology·Yixuan ZhaoQingfeng Li
Apr 23, 2017·Cell and Tissue Research·Cristina Has, Yinghong He
Sep 26, 2020·Nature Reviews. Disease Primers·Ajoy BardhanAdrian H Heagerty
Apr 5, 2020·The American Journal of Pathology·Eleanor Russell-Goldman, George F Murphy
Jan 14, 2018·Matrix Biology : Journal of the International Society for Matrix Biology·Patricia RousselleCécile Garnier
May 19, 2021·Cellular Signalling·Yasaswi Gayatri Mishra, Bramanandam Manavathi
Sep 23, 2021·The Journal of Cell Biology·Daisuke NanbaEmi K Nishimura

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