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...
| Egile Nagusiak: | , , , , , , , |
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| Formatua: | Journal article |
| Hizkuntza: | English |
| Argitaratua: |
Company of Biologists
2014
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| _version_ | 1826307316076511232 |
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| author | Weaver, SA Wolters, B Ito, N Woskowicz, A Kaneko, K Shitomi, Y Seiki, M Itoh, Y |
| author_facet | Weaver, SA Wolters, B Ito, N Woskowicz, A Kaneko, K Shitomi, Y Seiki, M Itoh, Y |
| author_sort | Weaver, SA |
| collection | OXFORD |
| 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. |
| first_indexed | 2024-03-07T07:01:22Z |
| format | Journal article |
| id | oxford-uuid:65f2c45c-9eca-40d8-9d4b-61e7282b7a93 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:01:22Z |
| publishDate | 2014 |
| publisher | Company of Biologists |
| record_format | dspace |
| spelling | oxford-uuid:65f2c45c-9eca-40d8-9d4b-61e7282b7a932022-03-29T17:17:03ZBasal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrixJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:65f2c45c-9eca-40d8-9d4b-61e7282b7a93EnglishSymplectic Elements at OxfordCompany of Biologists2014Weaver, SAWolters, BIto, NWoskowicz, AKaneko, KShitomi, YSeiki, MItoh, YThe 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. |
| spellingShingle | Weaver, SA Wolters, B Ito, N Woskowicz, A Kaneko, K Shitomi, Y Seiki, M Itoh, Y 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 |
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