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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·2014·Journal of Cell Science

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).”

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Authors
Weaver, S. A., Wolters, B., Ito, N., Woskowicz, A. M., Kaneko, K., Shitomi, Y., Seiki, M., & Itoh, Y.
Venue
Journal of Cell Science
Published
2014-01-01
ISSN
  • 1477-9137
  • 0021-9533
Cited by
15
References
0
Language
en

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