Lack of evidence for a role of anthrax toxin receptors as surface receptors for collagen VI and for its cleaved-off C5 domain/endotrophin

Matthias Przyklenk; Stefanie Elisabeth Heumüller; Carolin Freiburg; Steffen Lütke; Gerhard Sengle; Manuel Koch; Mats Paulsson; Alvise Schiavinato; Raimund Wagener

doi:10.1016/j.isci.2022.105116

Lack of evidence for a role of anthrax toxin receptors as surface receptors for collagen VI and for its cleaved-off C5 domain/endotrophin

iScience. 2022 Sep 12;25(10):105116. doi: 10.1016/j.isci.2022.105116. eCollection 2022 Oct 21.

Authors

Matthias Przyklenk¹, Stefanie Elisabeth Heumüller¹, Carolin Freiburg¹, Steffen Lütke¹, Gerhard Sengle^{1

2

3

4}, Manuel Koch^{1

4

5}, Mats Paulsson^{1

3

4}, Alvise Schiavinato^{1

2

6}, Raimund Wagener^{1

3}

Affiliations

¹ Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
² Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
³ Cologne Center for Musculoskeletal Biomechanics (CCMB), Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
⁴ Center for Molecular Medicine Cologne (CMMC), University of Cologne, Cologne, Germany.
⁵ Institute for Dental Research and Oral Musculoskeletal Biology, Medical Faculty, University of Cologne, Cologne, Germany.
⁶ Istituto Di Patologia Clinica, Azienda Sanitaria Universitaria Integrata di Udine (ASUID), Udine, Italy.

Abstract

The microfibril-forming collagen VI is proteolytically cleaved and it was proposed that the released C-terminal Kunitz domain (C5) of the α3 chain is an adipokine important for tumor progression and fibrosis. Designated "endotrophin," C5 is a potent biomarker for fibroinflammatory diseases. However, the biochemical mechanisms behind endotrophin activity were not investigated. Earlier, anthrax toxin receptor 1 was found to bind C5, but this potential interaction was not further studied. Given the proposed physiological role of endotrophin, we aimed to determine how the signal is transmitted. Surprisingly, we could not detect any interaction between endotrophin and anthrax toxin receptor 1 or its close relative, anthrax toxin receptor 2. Moreover, we detect no binding of fully assembled collagen VI to either receptor. We also studied the collagen VI receptor NG2 (CSPG4) and confirmed that NG2 binds assembled collagen VI, but not cleaved C5/endotrophin. A cellular receptor for C5/endotrophin, therefore, still remains elusive.

Keywords: Cell biology; functional aspects of cell biology.