4.5 Article

The Missing Protein: Is T-Cadherin a Previously Unknown GPI-Anchored Receptor on Platelets?

Journal

MEMBRANES
Volume 11, Issue 3, Pages -

Publisher

MDPI
DOI: 10.3390/membranes11030218

Keywords

platelets; T-cadherin; cadherin-13; GPI-anchored protein

Funding

  1. RFBR [18-015-00372]
  2. Russian Federation [MK-3144.2019.7]

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This study provided evidence supporting the presence of T-cadherin on platelets. The glycosylphosphatidylinositol anchor in the platelet T-cadherin form was confirmed. Furthermore, the study characterized T-cadherin with post-translational modifications as a new GPI-anchored protein on human platelets.
The membrane of platelets contains at least one uncharacterized glycosylphosphatidylinositol (GPI)-anchored protein according to the literature. Moreover, there is not enough knowledge on the receptor of low-density lipoproteins (LDL) mediating rapid Ca2+ signaling in platelets. Coincidentally, expression of a GPI-anchored protein T-cadherin increases LDL-induced Ca2+ signaling in nucleated cells. Here we showed evidence that supports the hypothesis about the presence of T-cadherin on platelets. The presence of T-cadherin on the surface of platelets and megakaryocytes was proven using antibodies whose specificity was tested on several negative and positive control cells by flow cytometry and confocal microscopy. Using phosphatidylinositol-specific phospholipase C, the presence of glycosylphosphatidylinositol anchor in the platelet T-cadherin form as well as in other known forms was confirmed. We showed by immunoblotting that the significant part of T-cadherin was detected in specific membrane domains (detergent Triton X-114 resistant) and the molecular weight of this newly identified protein was greater than that of T-cadherin from nucleated cells. Nevertheless, polymerase chain reaction data confirmed only the presence of isoform-1 of T-cadherin in platelets and megakaryocytes, which was also present in nucleated cells. We observed the redistribution of this newly identified protein after the activation of platelets, but only further work may explain its functional importance. Thus, our data described T-cadherin with some post-translational modifications as a new GPI-anchored protein on human platelets.

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