Fig. 9
From: Variants in exons 5 and 6 of ACTB cause syndromic thrombocytopenia
Proposed model of the mechanisms underlying thrombocytopenia in ACTB-AST. Preplatelets and barbell-shaped platelets shed into the blood stream convert into platelets in a microtubule-dependent manner. A thick band of microtubules is responsible for twisting the center of the preplatelet to form the barbell-shaped platelet, essentially dividing it into two individual terminal platelets. Abscission of terminal platelets subsequently occurs in the circulation. In ACTB-AST patients, cytoplasmic actin isoforms and select ABPs (α-actinin 1, NM-2A and to a lesser extent Filamin A) enrich at the preplatelet cortex. The cortical microtubule band observed in mature control cells forms in fewer ACTB-AST platelets. Instead, microtubules are highly disordered. We propose that the final platelet processing steps are therefore restricted in preplatelets with a disordered microtubule cytoskeleton, leading to reduced numbers of enlarged and immature platelets in patient circulation
