Role of dystrophins and utrophins in platelet adhesion process

Abstract

SummaryPlatelets are crucial at the site of vascular injury, adhering to the sub‐endothelial matrix through receptors on their surface, leading to cell activation and aggregation to form a haemostatic plug. Platelets display focal adhesions as well as stress fibres to contract and facilitate expulsion of growth and pro‐coagulant factors contained in the granules and to constrict the clot. The interaction of F‐actin with different actin‐binding proteins determines the properties and composition of the focal adhesions. Recently, we demonstrated the presence of dystrophin‐associated protein complex corresponding to short dystrophin isoforms (Dp71d and Dp71) and the uthophin gene family (Up400 and Up71), which promote shape change, adhesion, aggregation, and granule centralisation. To elucidate participation of both complexes during the platelet adhesion process, their potential association with integrin β‐1 fraction and the focal adhesion system (α‐actinin, vinculin and talin) was evaluated by immunofluorescence and immunoprecipitation assays. It was shown that the short dystrophin‐associated protein complex participated in stress fibre assembly and in centralisation of cytoplasmic granules, while the utrophin‐associated protein complex assembled and regulated focal adhesions. The simultaneous presence of dystrophin and utrophin complexes indicates complementary structural and signalling mechanisms to the actin network, improving the platelet haemostatic role.

TAPP2 links phosphoinositide 3-kinase signaling to B-cell adhesion through interaction with the cytoskeletal protein utrophin: expression of a novel cell adhesion-promoting complex in B-cell leukemia

“…48,49 A series of studies have implicated utrophin as well as a differentially spliced short form of dystrophin in integrinmediated platelet aggregation. 34,50,51 In adhering platelets, utrophin was found to localize in plasma membrane patches and focal adhesions, and coprecipitated with focal adhesionassociated proteins such as ␣-actinin and focal ahesion kinase. 34 Integrin-mediated platelet activation is known to be PI3K dependent and shares many signaling mechanisms in common with lymphocytes.…”

“…34,50,51 In adhering platelets, utrophin was found to localize in plasma membrane patches and focal adhesions, and coprecipitated with focal adhesionassociated proteins such as ␣-actinin and focal ahesion kinase. 34 Integrin-mediated platelet activation is known to be PI3K dependent and shares many signaling mechanisms in common with lymphocytes. 52,53 Intriguingly, one study found that integrin activation of platelets leads to preferential production of PI(3,4)P2, 54 suggesting that PI(3,4)P2 effector proteins such as the TAPPs may be involved.…”

“…In nonlymphoid cells, utrophin/syntrophin complexes are known to play important roles in cell-matrix adhesive interactions. 34,35,39 We For personal use only. on April 7, 2019.…”

“…34,35 We therefore examined whether TAPP2 can regulate cell adhesion to matrix proteins. We established adhesion assay conditions that can distinguish substantial activation-induced increases in B-lymphoma cell adhesion ( Figure 6A).…”

Dystrophin–Glycoprotein Complex in Blood Cells

“…Apparently, in order to fulill this hemosatic role, the coexistence of the DGC composed of short dystrophins or utrophins plays both a structural role in participation in stress-iber assembly and in the centralization of cytoplasmic granules, and a regulatory role, incorporating FAK into the complex. The coexistence of dystrophin and utrophin complexes indicates structural and signaling mechanisms that are complementary to the actin network during the adhesion process [48] (Figure 1). …”