ArticleBlood2016
Synthesis and dephosphorylation of MARCKS in the late stages of megakaryocyte maturation drive proplatelet formation.
Article in Blood, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 46 citations in OpenAlex.
- Aging changes the mechanism that underlies JAK2 modulation of neutrophil function.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- ER-associated degradation pathway protein SEL1L plays an evolutionarily conserved role in platelet adhesion.The Journal of clinical investigation · 2026Article
- Induction of moderate DNA damage enhances megakaryopoiesis and platelet production.Blood advances · 2026Article
- MARCKS N-terminal sequence-derived inhibitor peptides impair monocytic ROS production and migration via MARCKS-independent effects.Molecular biology reports · 2025Article
- MARCKS protein is a potential target in a naturally occurring equine model of neutrophilic asthma.Respiratory research · 2025Article
- Regulating mitochondrial oxidative phosphorylation and MAPK signaling: wedelolactone as a novel therapeutic for radiation-induced thrombocytopenia.Frontiers in pharmacology · 2025Article
- Lung megakaryocytes engulf inhaled airborne particles to promote intrapulmonary inflammation and extrapulmonary distribution.Nature communications · 2024Article
- Evidence for a cytoplasmic proplatelet promoting factor that triggers platelet production.Haematologica · 2024Article
- Cell cycle-dependent centrosome clustering precedes proplatelet formation.Science advances · 2024Article
- Quantitative label-free mass spectrometry reveals content and signaling differences between neonatal and adult platelets.Journal of thrombosis and haemostasis : JTH · 2024Article
- Article
- Critical shifts in lipid metabolism promote megakaryocyte differentiation and proplatelet formation.Nature cardiovascular research · 2023Article
- Efficient megakaryopoiesis and platelet production require phospholipid remodeling and PUFA uptake through CD36.Nature cardiovascular research · 2023Article
- Article
- CLEC5A and TLR2 are critical in SARS-CoV-2-induced NET formation and lung inflammation.Journal of biomedical science · 2022Article
- Sequence-specific 2'-O-methoxyethyl antisense oligonucleotides activate human platelets through glycoprotein VI, triggering formation of platelet-leukocyte aggregates.Haematologica · 2022Article
- Activation of PTH1R alleviates epididymitis and orchitis through Gq and β-arrestin-1 pathways.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Pathophysiological roles of myristoylated alanine-rich C-kinase substrate (MARCKS) in hematological malignancies.Biomarker research · 2021Review
- Novel gene variants in patients with platelet-based bleeding using combined exome sequencing and RNAseq murine expression data.Journal of thrombosis and haemostasis : JTH · 2021Article
- Is there a role for the ACE2 receptor in SARS-CoV-2 interactions with platelets?Journal of thrombosis and haemostasis : JTH · 2021Review
Corrections and comments
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Authors and funding
13 authors at 4 institutions in 1 country.
Funding
Abstract
Platelets are essential for hemostasis, and thrombocytopenia is a major clinical problem. Megakaryocytes (MKs) generate platelets by extending long processes, proplatelets, into sinusoidal blood vessels. However, very little is known about what regulates proplatelet formation. To uncover which proteins were dynamically changing during this process, we compared the proteome and transcriptome of round vs proplatelet-producing MKs by 2D difference gel electrophoresis (DIGE) and polysome profiling, respectively. Our data revealed a significant increase in a poorly-characterized MK protein, myristoylated alanine-rich C-kinase substrate (MARCKS), which was upregulated 3.4- and 5.7-fold in proplatelet-producing MKs in 2D DIGE and polysome profiling analyses, respectively. MARCKS is a protein kinase C (PKC) substrate that binds PIP2. In MKs, it localized to both the plasma and demarcation membranes. MARCKS inhibition by peptide significantly decreased proplatelet formation 53%. To examine the role of MARCKS in the PKC pathway, we treated MKs with polymethacrylate (PMA), which markedly increased MARCKS phosphorylation while significantly inhibiting proplatelet formation 84%, suggesting that MARCKS phosphorylation reduces proplatelet formation. We hypothesized that MARCKS phosphorylation promotes Arp2/3 phosphorylation, which subsequently downregulates proplatelet formation; both MARCKS and Arp2 were dephosphorylated in MKs making proplatelets, and Arp2 inhibition enhanced proplatelet formation. Finally, we used MARCKS knockout (KO) mice to probe the direct role of MARCKS in proplatelet formation; MARCKS KO MKs displayed significantly decreased proplatelet levels. MARCKS expression and signaling in primary MKs is a novel finding. We propose that MARCKS acts as a "molecular switch," binding to and regulating PIP2 signaling to regulate processes like proplatelet extension (microtubule-driven) vs proplatelet branching (Arp2/3 and actin polymerization-driven).
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Registered trials
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