Abstract
The platelet and megakaryocyte cytoskeletons are essential for formation and function of these cells. A dynamic, properly organised tubulin and actin cytoskeleton is critical for the development of the megakaryocyte and the extension of proplatelets. Tubulin in particular plays a pivotal role in the extension of these proplatelets and the release of platelets from them. Tubulin is further required for the maintenance of platelet size, and actin is the driving force for shape change, spreading and platelet contraction during platelet activation. Whilst several key proteins which regulate these cytoskeletons have been described in detail, the formin family of proteins has received less attention. Formins are intriguing as, although they were initially believed to simply be a nucleator of actin polymerisation, increasing evidence shows they are important regulators of the crosstalk between the actin and microtubule cytoskeletons. In this review, we will introduce the formin proteins and consider the recent evidence that they play an important role in platelets and megakaryocytes in mediating both the actin and tubulin cytoskeletons.
Highlights
Formin proteins were first identified in mice from studies on abnormal limb development [1,2] with homologues subsequently being found in drosophila and yeast [3]
Formins have the ability to both nucleate and accelerate the elongation of linear actin filaments. They play a crucial role in the assembly of cytoskeletal structures such as filopodia, lamellipodia and stress fibres and are required for a range of cellular processes including cell adhesion, cell division and cell motility [4]. These multidomain proteins are defined by the presence of highly conserved Formin Homology 1 (FH1) and Formin Homology 2 (FH2) domains and a less well-conserved FH3 domain (Figure 1(a))
In its active form, it is a potent actin nucleator and accelerates filament elongation. mDia1 is activated as described above by GTP bound Rho GTPase binding to the GTPase-binding domain (GBD) causing displacement of the Diaphanous Auto-regulatory Domain (DAD) domain from the N terminal region of mDia1
Summary
Formin proteins were first identified in mice from studies on abnormal limb development [1,2] with homologues subsequently being found in drosophila and yeast [3]. We will introduce the formin proteins and consider the recent evidence that they play an important role in platelets and megakaryocytes in mediating both the actin and tubulin cytoskeletons.
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