Søren Kragh Moestrup

Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

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Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2. / Johanns, Manuel; Lemoine, Pascale; Janssens, Virginie; Grieco, Giuseppina; Moestrup, Soren K; Nielsen, Rikke; Christensen, Erik I; Courtoy, Pierre J; Emonard, Herve; Marbaix, Etienne; Henriet, Patrick.

In: Scientific Reports, Vol. 7, No. 1, 28.06.2017, p. 4328.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Harvard

Johanns, M, Lemoine, P, Janssens, V, Grieco, G, Moestrup, SK, Nielsen, R, Christensen, EI, Courtoy, PJ, Emonard, H, Marbaix, E & Henriet, P 2017, 'Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2', Scientific Reports, vol. 7, no. 1, pp. 4328. https://doi.org/10.1038/s41598-017-04648-y

APA

Johanns, M., Lemoine, P., Janssens, V., Grieco, G., Moestrup, S. K., Nielsen, R., Christensen, E. I., Courtoy, P. J., Emonard, H., Marbaix, E., & Henriet, P. (2017). Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2. Scientific Reports, 7(1), 4328. https://doi.org/10.1038/s41598-017-04648-y

CBE

Johanns M, Lemoine P, Janssens V, Grieco G, Moestrup SK, Nielsen R, Christensen EI, Courtoy PJ, Emonard H, Marbaix E, Henriet P. 2017. Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2. Scientific Reports. 7(1):4328. https://doi.org/10.1038/s41598-017-04648-y

MLA

Vancouver

Author

Johanns, Manuel ; Lemoine, Pascale ; Janssens, Virginie ; Grieco, Giuseppina ; Moestrup, Soren K ; Nielsen, Rikke ; Christensen, Erik I ; Courtoy, Pierre J ; Emonard, Herve ; Marbaix, Etienne ; Henriet, Patrick. / Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2. In: Scientific Reports. 2017 ; Vol. 7, No. 1. pp. 4328.

Bibtex

@article{dabf131cf3064b7ba3cd91f24ad8d6c8,
title = "Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2",
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.",
keywords = "Journal Article",
author = "Manuel Johanns and Pascale Lemoine and Virginie Janssens and Giuseppina Grieco and Moestrup, {Soren K} and Rikke Nielsen and Christensen, {Erik I} and Courtoy, {Pierre J} and Herve Emonard and Etienne Marbaix and Patrick Henriet",
year = "2017",
month = jun,
day = "28",
doi = "10.1038/s41598-017-04648-y",
language = "English",
volume = "7",
pages = "4328",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

RIS

TY - JOUR

T1 - Cellular uptake of proMMP-2:TIMP-2 complexes by the endocytic receptor megalin/LRP-2

AU - Johanns, Manuel

AU - Lemoine, Pascale

AU - Janssens, Virginie

AU - Grieco, Giuseppina

AU - Moestrup, Soren K

AU - Nielsen, Rikke

AU - Christensen, Erik I

AU - Courtoy, Pierre J

AU - Emonard, Herve

AU - Marbaix, Etienne

AU - Henriet, Patrick

PY - 2017/6/28

Y1 - 2017/6/28

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/s41598-017-04648-y

DO - 10.1038/s41598-017-04648-y

M3 - Journal article

C2 - 28659595

VL - 7

SP - 4328

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

ER -