دورية أكاديمية
Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2
| العنوان: | Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2 |
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| المؤلفون: | Manuel Johanns, Pascale Lemoine, Virginie Janssens, Giuseppina Grieco, Soren K. Moestrup, Rikke Nielsen, Erik I. Christensen, Pierre J. Courtoy, Hervé Emonard, Etienne Marbaix, Patrick Henriet |
| المصدر: | Scientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) |
| بيانات النشر: | Nature Portfolio, 2017. |
| سنة النشر: | 2017 |
| المجموعة: | LCC:Medicine LCC:Science |
| مصطلحات موضوعية: | Medicine, Science |
| الوصف: | Abstract Matrix metalloproteinases (MMPs) are regulated at multiple transcriptional and post-transcriptional levels, among which receptor-mediated endocytic clearance. We previously showed that low-density lipoprotein receptor-related protein-1 (LRP-1) mediates the clearance of a complex between the zymogen form of MMP-2 (proMMP-2) and tissue inhibitor of metalloproteinases, TIMP-2, in HT1080 human fibrosarcoma cells. Here we show that, in BN16 rat yolk sac cells, proMMP-2:TIMP-2 complex is endocytosed through a distinct LRP member, megalin/LRP-2. Addition of receptor-associated protein (RAP), a natural LRP antagonist, caused accumulation of endogenous proMMP-2 and TIMP-2 in conditioned media. Incubation with RAP also inhibited membrane binding and cellular uptake of exogenous iodinated proMMP-2:TIMP-2. Moreover, antibodies against megalin/LRP-2, but not against LRP-1, inhibited binding of proMMP-2:TIMP-2 to BN16 cell surface. BIAcore analysis confirmed direct interaction between the complex and megalin/LRP-2. Conditional renal invalidation of megalin/LRP-2 in mice resulted in accumulation of proMMP-2 and TIMP-2 in their urine, highlighting the physiological relevance of the binding. We conclude that megalin/LRP-2 can efficiently mediate cell-surface binding and endocytosis of proMMP-2:TIMP-2 complex. Therefore megalin/LRP-2 can be considered as a new actor in regulation of MMP-2 activity, an enzyme crucially involved in many pathological processes. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2045-2322 |
| العلاقة: | https://doaj.org/toc/2045-2322Test |
| DOI: | 10.1038/s41598-017-04648-y |
| الوصول الحر: | https://doaj.org/article/ef8ab5cbd1544d42a3b9b4dc04fabb65Test |
| رقم الانضمام: | edsdoj.f8ab5cbd1544d42a3b9b4dc04fabb65 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 20452322 |
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| DOI: | 10.1038/s41598-017-04648-y |