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Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix
The membrane-anchored collagenase membrane type 1 matrix metalloprotease (MT1-MMP) has been shown to play an essential role during epithelial tubulogenesis in 3D collagen matrices; however, its regulation during tubulogenesis is not understood. Here, we report that degradation of collagen in polariz...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Company of Biologists
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117704/ https://www.ncbi.nlm.nih.gov/pubmed/24463815 http://dx.doi.org/10.1242/jcs.135236 |
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author | Weaver, Sarah A. Wolters, Brit Ito, Noriko Woskowicz, Anna M. Kaneko, Kazuyo Shitomi, Yasuyuki Seiki, Motoharu Itoh, Yoshifumi |
author_facet | Weaver, Sarah A. Wolters, Brit Ito, Noriko Woskowicz, Anna M. Kaneko, Kazuyo Shitomi, Yasuyuki Seiki, Motoharu Itoh, Yoshifumi |
author_sort | Weaver, Sarah A. |
collection | PubMed |
description | The membrane-anchored collagenase membrane type 1 matrix metalloprotease (MT1-MMP) has been shown to play an essential role during epithelial tubulogenesis in 3D collagen matrices; however, its regulation during tubulogenesis is not understood. Here, we report that degradation of collagen in polarized epithelial cells is post-translationally regulated by changing the localization of MT1-MMP from the apical to the basal surface. MT1-MMP predominantly localizes at the apical surface in inert polarized epithelial cells, whereas treatment with HGF induced basal localization of MT1-MMP followed by collagen degradation. The basal localization of MT1-MMP requires the ectodomains of the enzyme because deletion of the MT-loop region or the hemopexin domain inhibited basal localization of the enzyme. TGFβ is a well-known inhibitor of tubulogenesis and our data indicate that its mechanism of inhibition is, at least in part, due to inhibition of MT1-MMP localization to the basal surface. Interestingly, however, the effect of TGFβ was found to be bi-phasic: at high doses it effectively inhibited basal localization of MT1-MMP, whereas at lower doses tubulogenesis and basal localization of MT1-MMP was promoted. Taken together, these data indicate that basal localization of MT1-MMP is a key factor promoting the degradation of extracellular matrix by polarized epithelial cells, and that this is an essential part of epithelial morphogenesis in 3D collagen. |
format | Online Article Text |
id | pubmed-4117704 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Company of Biologists |
record_format | MEDLINE/PubMed |
spelling | pubmed-41177042015-03-15 Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix Weaver, Sarah A. Wolters, Brit Ito, Noriko Woskowicz, Anna M. Kaneko, Kazuyo Shitomi, Yasuyuki Seiki, Motoharu Itoh, Yoshifumi J Cell Sci Research Article The membrane-anchored collagenase membrane type 1 matrix metalloprotease (MT1-MMP) has been shown to play an essential role during epithelial tubulogenesis in 3D collagen matrices; however, its regulation during tubulogenesis is not understood. Here, we report that degradation of collagen in polarized epithelial cells is post-translationally regulated by changing the localization of MT1-MMP from the apical to the basal surface. MT1-MMP predominantly localizes at the apical surface in inert polarized epithelial cells, whereas treatment with HGF induced basal localization of MT1-MMP followed by collagen degradation. The basal localization of MT1-MMP requires the ectodomains of the enzyme because deletion of the MT-loop region or the hemopexin domain inhibited basal localization of the enzyme. TGFβ is a well-known inhibitor of tubulogenesis and our data indicate that its mechanism of inhibition is, at least in part, due to inhibition of MT1-MMP localization to the basal surface. Interestingly, however, the effect of TGFβ was found to be bi-phasic: at high doses it effectively inhibited basal localization of MT1-MMP, whereas at lower doses tubulogenesis and basal localization of MT1-MMP was promoted. Taken together, these data indicate that basal localization of MT1-MMP is a key factor promoting the degradation of extracellular matrix by polarized epithelial cells, and that this is an essential part of epithelial morphogenesis in 3D collagen. The Company of Biologists 2014-03-15 /pmc/articles/PMC4117704/ /pubmed/24463815 http://dx.doi.org/10.1242/jcs.135236 Text en © 2014. Published by The Company of Biologists Ltd http://creativecommons.org/licenses/by/3.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Research Article Weaver, Sarah A. Wolters, Brit Ito, Noriko Woskowicz, Anna M. Kaneko, Kazuyo Shitomi, Yasuyuki Seiki, Motoharu Itoh, Yoshifumi Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix |
title | Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix |
title_full | Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix |
title_fullStr | Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix |
title_full_unstemmed | Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix |
title_short | Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix |
title_sort | basal localization of mt1-mmp is essential for epithelial cell morphogenesis in 3d collagen matrix |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4117704/ https://www.ncbi.nlm.nih.gov/pubmed/24463815 http://dx.doi.org/10.1242/jcs.135236 |
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