Przyklenk Matthias, Heumüller Stefanie Elisabeth, Freiburg Carolin, Lütke Steffen, Sengle Gerhard, Koch Manuel, Paulsson Mats, Schiavinato Alvise, Wagener Raimund
Center for Biochemistry, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
Department of Pediatrics and Adolescent Medicine, Faculty of Medicine and University Hospital Cologne, University of Cologne, Cologne, Germany.
iScience. 2022 Sep 12;25(10):105116. doi: 10.1016/j.isci.2022.105116. eCollection 2022 Oct 21.
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.
形成微原纤维的胶原蛋白VI会被蛋白水解切割，有人提出，α3链释放的C末端库尼茨结构域（C5）是一种对肿瘤进展和纤维化很重要的脂肪因子。C5被命名为“内营养蛋白”，是纤维炎性疾病的一种有效生物标志物。然而，内营养蛋白活性背后的生化机制尚未得到研究。早些时候，发现炭疽毒素受体1与C5结合，但这种潜在的相互作用没有进一步研究。鉴于内营养蛋白的假定生理作用，我们旨在确定信号是如何传递的。令人惊讶的是，我们没有检测到内营养蛋白与炭疽毒素受体1或其近亲炭疽毒素受体2之间的任何相互作用。此外，我们没有检测到完全组装好的胶原蛋白VI与任何一种受体的结合。我们还研究了胶原蛋白VI受体NG2（CSPG4），并证实NG2与组装好的胶原蛋白VI结合，但不与切割后的C5/内营养蛋白结合。因此，C5/内营养蛋白的细胞受体仍然难以捉摸。
