The tubulin code in platelet biogenesis.

Kimmerlin, Quentin; Strassel, Catherine; Eckly, Anita; Lanza, François

doi:10.1016/j.semcdb.2022.01.010

Cited by 5 publications

(4 citation statements)

References 112 publications

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“…Ostensibly similar motor-driven microtubule looping is important for extrusion in platelet biogenesis from mega-karyocytes 19 resulting in a dynamic circumferential bundle of microtubules within platelets themselves. This characteristic bundle, called the marginal band, mechanically maintains the platelet discoid shape during their resting state and rapidly remodels under platelet activation 11 , 20 – 22 .…”

Section: Resultsmentioning

confidence: 99%

“…To explore the requirements for the formation of these structures, we utilise an in vitro reconstitution system which demonstrates that, although cofilin-bound F-actin can be incorporated into microtubules, cofilin is not essential. A dynamic and bundled microtubule cytoskeleton is present in native human platelets 11 and Focussed-Ion-Beam (FIB) milling and cryoET reveals that actin filaments with both cofilin-bound and canonical morphologies are found within platelet microtubules, providing an unequivocal identification of lumenal F-actin in a physiological setting that is not modified by small-molecule treatment.…”

Section: Introductionmentioning

confidence: 99%

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CryoET reveals actin filaments within platelet microtubules

Tsuji,

Bradshaw,

Allen

et al. 2024

Nat Commun

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Crosstalk between the actin and microtubule cytoskeletons is important for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear. Here, we show that the short-crossover Class I actin filament previously identified inside microtubules in human HAP1 cells is cofilin-bound F-actin. Lumenal F-actin can be reconstituted in vitro, but cofilin is not essential. Moreover, actin filaments with both cofilin-bound and canonical morphologies reside within human platelet microtubules under physiological conditions. We propose that stress placed upon the microtubule network during motor-driven microtubule looping and sliding may facilitate the incorporation of actin into microtubules.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CryoET reveals actin filaments within platelet microtubules

Tsuji,

Bradshaw,

Allen

et al. 2024

Nat Commun

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show abstract

“…Ostensibly similar motor-driven microtubule looping is important for extrusion in platelet biogenesis from mega-karyocytes [18] resulting in a dynamic circumferential bundle of microtubules within platelets themselves. This characteristic bundle, called the marginal band, mechanically maintains the platelet discoid shape during their resting state and rapidly remodels under platelet activation [11,[19][20][21].…”

Section: Resultsmentioning

confidence: 99%

“…To explore the requirements for the formation of these structures, we utilise an in vitro reconstitution system which demonstrates that, although cofilin-bound F-actin can incorporate into microtubules, cofilin is not essential. A dynamic and bundled microtubule cytoskeleton is present in native human platelets [11] and Focussed-Ion-Beam (FIB) milling and cryoET reveals that actin filaments with both cofilin-bound and canonical morphologies are found within platelet microtubules, providing an unequivocal identification of lumenal F-actin in a physiological setting that is not modified by small-molecule treatment.…”

Section: Introductionmentioning

confidence: 99%

CryoET reveals actin filaments within platelet microtubules

Tsuji,

Bradshaw,

Allen

et al. 2023

Preprint

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Crosstalk between the actin and microtubule cytoskeletons is essential for many cellular processes. Recent studies have shown that microtubules and F-actin can assemble to form a composite structure where F-actin occupies the microtubule lumen. Whether these cytoskeletal hybrids exist in physiological settings and how they are formed is unclear. Here, we show that the short-crossover Class I actin filament previously identified inside microtubules in human HAP1 cells is cofilin-bound F-actin. Lumenal F-actin can be reconstitutedin vitro, but cofilin is not essential. Moreover, actin filaments with both cofilin-bound and canonical morphologies reside within human platelet microtubules under physiological conditions. We propose that stress placed upon the microtubule network during motor-driven microtubule looping and sliding may facilitate the incorporation of actin into microtubules.

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Mechanical confinement prevents ectopic platelet release

Guinard,

Brassard-Jollive,

Ruch

et al. 2024

Proc. Natl. Acad. Sci. U.S.A.

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Blood platelets are produced by megakaryocytes (MKs), their parent cells, which are in the bone marrow. Once mature, MK pierces through the sinusoid vessel, and the initial protrusion further elongates as proplatelet or buds to release platelets. The mechanisms controlling the decision to initiate proplatelet and platelet formation are unknown. Here, we show that the mechanical properties of the microenvironment prevent proplatelet and platelet release in the marrow stroma while allowing this process in the bloodstream. Loss of marrow confinement following myelosuppression led to inappropriate proplatelet and platelet release into the extravascular space. We further used an inert viscoelastic hydrogel to evaluate the impact of compressive stress. Transcriptional analysis showed that culture in three-dimensional gel induced upregulation of genes related to the Rho-GTPase pathway. We found higher Rho-GTPase activation, myosin light chain phosphorylation and F-actin under mechanical constraints while proplatelet formation was inhibited. The use of latrunculin-A to decrease F-actin promoted microtubule-dependent budding and proplatelet extension inside the gel. Additionally, ex vivo exposure of intact bone marrow to latrunculin-A triggered proplatelet extensions in the interstitial space. In vivo, this confinement-mediated high intracellular tension is responsible for the formation of the peripheral zone, a unique actin-rich structure. Cytoskeleton reorganization induces the disappearance of the peripheral zone upon reaching a liquid milieu to facilitate proplatelet and platelet formation. Hence, our data provide insight into the mechanisms preventing ectopic platelet release in the marrow stroma. Identifying such pathways is especially important for understanding pathologies altering marrow mechanics such as chemotherapy or myelofibrosis.

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The tubulin code in platelet biogenesis.

Cited by 5 publications

References 112 publications

CryoET reveals actin filaments within platelet microtubules

CryoET reveals actin filaments within platelet microtubules

CryoET reveals actin filaments within platelet microtubules

Mechanical confinement prevents ectopic platelet release

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