New insights into cytoskeletal remodeling during platelet production

Ghalloussi, Dorsaf; Dhenge, Ankita; Bergmeier, Wolfgang

doi:10.1111/jth.14544

Cited by 34 publications

(26 citation statements)

References 111 publications

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“…17 in Table 1 and Figure 1 ) ( 91 ). The cytoskeletal defects of megakaryocytes are responsible for the low number of platelets in patients with WAS ( 92 ). WASP deficiency promotes T-cell cytoskeletal tension decay and phosphorylation of a serine/threonine protein kinase 4 (STK4) that usually increase T-cell migration, therefore promoting immune synapse breaking and secondary B cells dysfunction ( 93 , 94 ).…”

Section: Introductionmentioning

confidence: 99%

Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation

et al. 2021

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A growing number of monogenic immune-mediated diseases have been related to genes involved in pathways of actin cytoskeleton remodeling. Increasing evidences associate cytoskeleton defects to autoinflammatory diseases and primary immunodeficiencies. We reviewed the pathways of actin cytoskeleton remodeling in order to identify inflammatory and immunological manifestations associated to pathological variants. We list more than twenty monogenic diseases, ranging from pure autoinflammatory conditions as familial Mediterranean fever, mevalonate kinase deficiency and PAPA syndrome, to classic and novel primary immunodeficiencies as Wiskott-Aldrich syndrome and DOCK8 deficiency, characterized by the presence of concomitant inflammatory and autoimmune manifestations, such as vasculitis and cytopenia, to severe and recurrent infections. We classify these disorders according to the role of the mutant gene in actin cytoskeleton remodeling, and in particular as disorders of transcription, elongation, branching and activation of actin. This expanding field of rare immune disorders offers a new perspective to all immunologists to better understand the physiological and pathological role of actin cytoskeleton in cells of innate and adaptive immunity.

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Section: Introductionmentioning

confidence: 99%

Actin Remodeling Defects Leading to Autoinflammation and Immune Dysregulation

et al. 2021

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“…Based on in vitro experiments, several cytoskeletal elements have been identified as playing a major role. 22 , 23 Inside cPPT, the microtubules are organized as linear bundles of mixed polarity running along the shaft and ending as a coil in the cPPT bud, prefiguring the platelet marginal band. 2 , 17 , 24 Incubating MK in vitro in the presence of microtubule depolymerizing drugs prevented de novo cPPT extension 17 , 21 , 25 , 26 and retracted already formed cPPT.…”

Section: Introductionmentioning

confidence: 99%

Cytoskeletal-based mechanisms differently regulate <i>in vivo</i> and <i>in vitro</i> proplatelet formation

et al. 2020

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Platelets are produced by bone marrow megakaryocytes through cytoplasmic protrusions, named native proplatelets (nPPT), into blood vessels. Proplatelets also refer to protrusions observed in megakaryocyte culture (cPPT) that are morphologically different. Contrary to cPPT, the mechanisms of nPPT formation are poorly understood. We show here in living mice that nPPT elongation is in equilibrium between protrusive and retraction forces mediated by myosin-IIA. We also found, using WT and β1-tubulin-deficient mice, that microtubule behavior differs between cPPT and nPPT, being absolutely required in vitro, while less critical in vivo. Remarkably, microtubule depolymerization in myosin-deficient mice did not affect nPPT elongation. We then calculated that blood Stokes'forces may be sufficient to promote nPPT extension, independently of myosin and microtubules. Together, we propose a new mechanism for nPPT extension that might explain contradictions between severely affected cPPT production and moderate platelet count defects in some patients and animal models.

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“…This was probably due to the regulation of proplatelet formation through autocrine-paracrine signaling, 18,19 even though the exact mechanisms that drive proplatelet formation are still unknown. 20 Platelet-like particles could be found in the culture medium (►Supplementary Fig. S1, available in the online version).…”

Section: Resultsmentioning

confidence: 99%