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.
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| http://dx.doi.org/10.1016/j.isci.2022.105116 | DOI Listing |
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