LICAMM Unravelling the unusual secretory pathway of blood clotting factor XIII-A.

Summary

Clotting factor XIII-A is a member of the transglutaminase family of enzymes. Transglutaminases introduce covalent cross-links between other proteins, and in the case of FXIII-A, it cross-links the chains of fibrinogen to one another to stabilize blood clots. Transglutaminases are unusual in that, while they can be secreted from cells, they lack the signals required to direct them to the ER-Golgi pathway. Thus, they are among a small group of proteins that undergo unconventional secretion.

Recent studies have begun to clarify the pathways by which a few other unconventionally secreted proteins are released from cells, and we intend to apply the approaches that have emerged to understand the secretion of FXIII-A. Our recent studies have suggested that vascular macrophages secrete FXIII-A into the blood-stream and we will concentrate on isolating these cells, and establishing in vitro culture models under which cells adopt the characteristics of vascular macrophages.

References:

Association of coagulation factor XIII-A with Golgi proteins within monocyte-macrophages: implications for subcellular trafficking and secretion. Cordell PA et al (2010); Blood. 115 2674-81.

Cre/lox Studies Identify Resident Macrophages as the Major Source of Circulating Coagulation Factor XIII- A Beckers CML et al (2017);, Arteriosclerosis, Thrombosis, and Vascular Biology. 37 1494-1502

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