β‐Dystroglycan modulates the interplay between actin and microtubules in human‐adhered platelets

Abstract

To maintain the continuity of an injured blood vessel, platelets change shape, secrete granule contents, adhere, aggregate, and retract in a haemostatic plug. Ordered arrays of microtubules, microfilaments, and associated proteins are responsible for these platelet responses. In full-spread platelets, microfilament bundles in association with other cytoskeleton proteins are anchored in focal contacts. Recent studies in migrating cells suggest that co-ordination and direct physical interaction of microtubules and actin network modulate adhesion development. In platelets, we have proposed a feasible association between these two cytoskeletal systems, as well as the participation of the dystrophin-associated protein complex, as part of the focal adhesion complex. The present study analysed the participation of microtubules and actin during the platelet adhesion process. Confocal microscopy, fluorescence resonance transfer energy and immunoprecipitation assays were used to provide evidence of a cross-talk between these two cytoskeletal systems. Interestingly, beta-dystroglycan was found to act as an interplay protein between actin and microtubules and an additional communication between these two cytoskeleton networks was maintained through proteins of focal adhesion complex. Altogether our data are indicative of a dynamic co-participation of actin filaments and microtubules in modulating focal contacts to achieve platelet function.

Actin filaments and microtubule dual‐granule transport in human adhered platelets: the role of α‐dystrobrevins

“…Recently, using the microtubule‐inhibitor Col and the actin filament‐inhibitor CD, we found that microtubules and actin filaments were highly dependent upon each other, and that removing either component dramatically changed the organization of the other (Cerecedo et al , 2008). It is evident that platelet cell spreading requires extensive cellular remodelling, which was inhibited by treatment with CD or Col, as well as with jasplakinolide or taxol.…”

Dystrophin Dp71: The Smallest but Multifunctional Product of the Duchenne Muscular Dystrophy Gene

“…Later, the participation of Dp71-containing DAPC in actin-cytoskeleton remodeling of platelets was revealed [117], promoting shape change, adhesion, aggregation, and granule centralization. These authors also revealed that the platelet adhesion process requires the participation of microtubules and actin, and that the interplay between the two cytoskeletal systems is undertaken by β-DG and focal adhesion proteins [118]. Supporting the role of Dp71 in platelets, it was reported that adhesion to collagen in response to thrombin was significantly decreased in platelets isolated from mdx 3cv mice [119].…”

Loss of dystrophin and the microtubule‐binding protein ELP‐1 causes progressive paralysis and death of adult C. elegans

“…In addition to actin filaments, DGC components also interact with microtubules. For example, in non-muscle cells such as adhered platelets, β-dystroglycan alone interacts dynamically with both microtubules and actin filaments to modulate the formation of focal contacts (Cerecedo et al, 2008). Furthermore, both the vertebrate microtubule-actin cross-linking factor (MACF)—a hybrid of dystonin and a dystrophin-like plakin, and the Drosophila protein kakapo—a dystrophin-like plectin, each form essential links between microtubules, actin and integrin-based adhesion sites (Gregory and Brown, 1998; Leung et al, 1999; Leung et al, 2001; Sonnenberg and Liem, 2007).…”