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Basal localization of MT1-MMP is essential for epithelial cell morphogenesis in 3D collagen matrix.
Abstract
During epithelial tubulogenesis in 3D collagen matrices, the membrane-anchored collagenase MT1-MMP has been shown to play an essential role. 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. Inert polarized epithelial cells predominantly localized MT1-MMP at the apical surface, whereas HGF treatment induced basal localization of MT1-MMP, and resultant collagen degradation. The basal localization of MT1-MMP requires the ecto-domains of the enzyme, as 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 basal MT1-MMP localization. Interestingly, however, the effect of TGFβ was found to be bi-phasic: it effectively inhibited basal localization at high doses, but promoted basal localization of MT1-MMP and tubulogenesis at lower doses. Taken together these data indicate that basal localization of MT1-MMP is a key factor promoting ECM degradation by polarized epithelial cells, and that this is an essential part of epithelial morphogenesis in 3D collagen.
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Weaver et al. reported that the MT-loop, together with the hemopexin domain, is required for the translocation of MT1-MMP from the apical to the basal membrane in polarized epithelial cells during tubulogenesis, but deletion of the entire MT-loop has no significant effect on the expression, trafficking, processing, or the proteolytic activity of MT1-MMP.
“Weaver et al. reported that the MT-loop, together with the hemopexin domain, is required for the translocation of MT1-MMP from the apical to the basal membrane in polarized epithelial cells during tubulogenesis (65), but deletion of the entire MT-loop has no significant effect on the expression, trafficking, processing, or the proteolytic activity of MT1-MMP (61, 66).”
From Identification of amino acid residues in the MT-loop of MT1-MMP critical for its ability to cleave low-density lipoprotein receptor (2022) · cites this paper as [65]
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Wang, M., Alabi, A., Gu, H.-M., Gill, G., Zhang, Z., Jarad, S., Xia, X.-D., Shen, Y., Wang, G.-Q., & Zhang, D.-W. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.917238 · Cited by 13
Metadata
- Authors
- Weaver, S. A., Wolters, B., Ito, N., Woskowicz, A. M., Kaneko, K., Shitomi, Y., Seiki, M., & Itoh, Y.
- Venue
- Journal of Cell Science
- Publisher
- The Company of Biologists
- Published
- 2014-01-01
- ISSN
- 1477-9137
- 0021-9533
- PMC
- PMC4117704
- Cited by
- 15
- References
- 0
- Language
- en
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