The cartilage-specific lectin C-type lectin domain family 3 member A (CLEC3A) enhances tissue plasminogen activator-mediated plasminogen activation

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The cartilage-specific lectin C-type lectin domain family 3 member A (CLEC3A) enhances tissue plasminogen activator-mediated plasminogen activation. / Lau, Daniela; Elezagic, Dzemal; Hermes, Gabriele; Mörgelin, Matthias; Wohl, Alexander P.; Koch, Manuel; Hartmann, Ursula; Höllriegl, Stefan; Wagener, Raimund; Paulsson, Mats; Streichert, Thomas; Klatt, Andreas R.

In: Journal of Biological Chemistry, Vol. 293, No. 1, 2018, p. 203-214.

Research output: Contribution to journalArticle

Harvard

Lau, D, Elezagic, D, Hermes, G, Mörgelin, M, Wohl, AP, Koch, M, Hartmann, U, Höllriegl, S, Wagener, R, Paulsson, M, Streichert, T & Klatt, AR 2018, 'The cartilage-specific lectin C-type lectin domain family 3 member A (CLEC3A) enhances tissue plasminogen activator-mediated plasminogen activation', Journal of Biological Chemistry, vol. 293, no. 1, pp. 203-214. https://doi.org/10.1074/jbc.M117.818930

APA

CBE

Lau D, Elezagic D, Hermes G, Mörgelin M, Wohl AP, Koch M, Hartmann U, Höllriegl S, Wagener R, Paulsson M, Streichert T, Klatt AR. 2018. The cartilage-specific lectin C-type lectin domain family 3 member A (CLEC3A) enhances tissue plasminogen activator-mediated plasminogen activation. Journal of Biological Chemistry. 293(1):203-214. https://doi.org/10.1074/jbc.M117.818930

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Author

Lau, Daniela ; Elezagic, Dzemal ; Hermes, Gabriele ; Mörgelin, Matthias ; Wohl, Alexander P. ; Koch, Manuel ; Hartmann, Ursula ; Höllriegl, Stefan ; Wagener, Raimund ; Paulsson, Mats ; Streichert, Thomas ; Klatt, Andreas R. / The cartilage-specific lectin C-type lectin domain family 3 member A (CLEC3A) enhances tissue plasminogen activator-mediated plasminogen activation. In: Journal of Biological Chemistry. 2018 ; Vol. 293, No. 1. pp. 203-214.

RIS

TY - JOUR

T1 - The cartilage-specific lectin C-type lectin domain family 3 member A (CLEC3A) enhances tissue plasminogen activator-mediated plasminogen activation

AU - Lau, Daniela

AU - Elezagic, Dzemal

AU - Hermes, Gabriele

AU - Mörgelin, Matthias

AU - Wohl, Alexander P.

AU - Koch, Manuel

AU - Hartmann, Ursula

AU - Höllriegl, Stefan

AU - Wagener, Raimund

AU - Paulsson, Mats

AU - Streichert, Thomas

AU - Klatt, Andreas R.

PY - 2018

Y1 - 2018

N2 - C-type lectin domain family 3 member A (CLEC3A) is a poorly characterized protein belonging to the superfamily of C-type lectins. Its closest homologue tetranectin binds to the kringle 4 domain of plasminogen and enhances its association with tissue plasminogen activator (tPA) thereby enhancing plasmin production, but whether CLEC3A contributes to plasminogen activation is unknown. Here, we recombinantly expressed murine and human full-length CLEC3As as well as truncated forms of CLEC3A in HEK-293 Epstein-Barr nuclear antigen (EBNA) cells. We analyzed the structure of recombinant CLEC3A by SDS-PAGE and immunoblot, glycan analysis, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, size-exclusion chromatography, circular dichroism spectroscopy, and electron microscopy; compared the properties of the recombinant protein with those of CLEC3A extracted from cartilage; and investigated its tissue distribution and extracellular assembly by immunohistochemistry and immunofluorescence microscopy. We found that CLEC3A mainly occurs as a monomer, but also forms dimers and trimers, potentially via a coiled-coil α-helix. We also noted that CLEC3A can be modified with chondroitin/dermatan sulfate side chains and tends to oligomerize to form higher aggregates. We show that CLEC3A is present in resting, proliferating, and hypertrophic growth-plate cartilage and assembles into an extended extracellular network in cultures of rat chondrosarcoma cells. Further, we found that CLEC3A specifically binds to plasminogen and enhances tPA-mediated plasminogen activation. In summary, we have determined the structure, tissue distribution, and molecular function of the cartilage-specific lectin CLEC3A and show that CLEC3A binds to plasminogen and participates in tPA-mediated plasminogen activation.

AB - C-type lectin domain family 3 member A (CLEC3A) is a poorly characterized protein belonging to the superfamily of C-type lectins. Its closest homologue tetranectin binds to the kringle 4 domain of plasminogen and enhances its association with tissue plasminogen activator (tPA) thereby enhancing plasmin production, but whether CLEC3A contributes to plasminogen activation is unknown. Here, we recombinantly expressed murine and human full-length CLEC3As as well as truncated forms of CLEC3A in HEK-293 Epstein-Barr nuclear antigen (EBNA) cells. We analyzed the structure of recombinant CLEC3A by SDS-PAGE and immunoblot, glycan analysis, matrix-assisted laser desorption ionization time-of-flight mass spectrometry, size-exclusion chromatography, circular dichroism spectroscopy, and electron microscopy; compared the properties of the recombinant protein with those of CLEC3A extracted from cartilage; and investigated its tissue distribution and extracellular assembly by immunohistochemistry and immunofluorescence microscopy. We found that CLEC3A mainly occurs as a monomer, but also forms dimers and trimers, potentially via a coiled-coil α-helix. We also noted that CLEC3A can be modified with chondroitin/dermatan sulfate side chains and tends to oligomerize to form higher aggregates. We show that CLEC3A is present in resting, proliferating, and hypertrophic growth-plate cartilage and assembles into an extended extracellular network in cultures of rat chondrosarcoma cells. Further, we found that CLEC3A specifically binds to plasminogen and enhances tPA-mediated plasminogen activation. In summary, we have determined the structure, tissue distribution, and molecular function of the cartilage-specific lectin CLEC3A and show that CLEC3A binds to plasminogen and participates in tPA-mediated plasminogen activation.

U2 - 10.1074/jbc.M117.818930

DO - 10.1074/jbc.M117.818930

M3 - Article

VL - 293

SP - 203

EP - 214

JO - Journal of Biological Chemistry

T2 - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 1083-351X

IS - 1

ER -