F11R/JAM-A: why do platelets express a molecule which is also present in tight junctions?

F11 receptor (F11R)/Junctional Adhesion Molecule -A (JAM-A) is a transmembrane protein which belongs to the immunoglobulin superfamily of cell adhesion molecules. F11R/JAM-A is present in epithelial cells, endothelial cells, leukocytes, and blood platelets. In epithelial and endothelial cells, it takes part in the formation of tight junctions. In these structures, molecules of F11R/JAM-A located on adjacent cells form homodimers and thus take part in stabilization of cellular layer integrity. In leukocytes, F11R/JAM-A was shown to play role in their transmigration through the vascular wall. Paradoxically, the function of F11R/JAM-A in blood platelets, where it was primarily discovered, is much less understood. It has been proven to regulate downstream signaling of alpha IIb beta 3 integrin and to mediate platelet adhesion under static conditions. It was also shown to contribute to transient interactions of platelets with inflamed vascular wall. The review is aimed at summarizing the current state of knowledge of the platelet pool of F11R/JAM-A. The article also presents perspectives of the future research to better understand the role of this protein in hemostasis, thrombosis, and other processes where blood platelets are involved. Plain Language Summary The molecule of a complex name F11R/JAM-A is a protein which was primarily discovered on blood platelets. Later, the presence of the same molecule was confirmed on endothelial cells and epithelial cells. From the moment of the discovery, most of the research was focused on the role of this protein in the latter types of cells. It was found to be an important element of so-called tight junctions. These structures are crucial for maintaining of integrity and selective permeability of cellular layers composed of these types of cells. In the following years, the presence of F11R/JAM-A has also been reported on leukocytes. An important role of specific type of leukocytes is their penetration to the sites of inflammation. Interplay of F11R/JAM-A present on endothelium and that on leukocyte is involved in this process. But what about the role of this protein in blood platelets where it was originally discovered? There is limited knowledge regarding this issue. It was found to play a role in the ability of platelets to adhere to a surface under static conditions, but it is not known if the same is true under flow. Is the protein necessary for platelets to aggregate and form thrombus? Genetically engineered mice were created which lack this protein in blood platelets to answer this question. These platelets were abnormally reactive, as it transpired that the protein plays a role of a negative regulator to one of the most important mechanisms, which triggers platelet aggregation. But is this inhibitory function the only task F11R/JAM-A has to fulfil in platelets? Presented review collects all the knowledge regarding this protein in blood platelets and tries to show interesting routes which need exploration.