ArticleJournal of thrombosis and haemostasis : JTH2016
Non-genomic activities of retinoic acid receptor alpha control actin cytoskeletal events in human platelets.
Article in Journal of thrombosis and haemostasis : JTH, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 25 citations in OpenAlex.
- NR4A1 Acts as a Novel Regulator of Platelet Activation and Thrombus Formation.Circulation research · 2025Article
- A regulatory circuit controlled by extranuclear and nuclear retinoic acid receptor α determines T cell activation and function.Immunity · 2023Article
- A New Role of NAP1L1 in Megakaryocytes and Human Platelets.International journal of molecular sciences · 2022Article
- Human platelets display dysregulated sepsis-associated autophagy, induced by altered LC3 protein-protein interaction of the Vici-protein EPG5.Autophagy · 2022Article
- A ligand-independent fast function of RARα promotes exit from metabolic quiescence upon T cell activation and controls T cell differentiation.Mucosal immunology · 2021Article
- Human megakaryocytes possess intrinsic antiviral immunity through regulated induction of IFITM3.Blood · 2019Article
- Cobimetinib and trametinib inhibit platelet MEK but do not cause platelet dysfunction.Platelets · 2019Article
- Non-genomic effects of nuclear receptors: insights from the anucleate platelet.Cardiovascular research · 2018Review
- Granzyme A in Human Platelets Regulates the Synthesis of Proinflammatory Cytokines by Monocytes in Aging.Journal of immunology (Baltimore, Md. : 1950) · 2018Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
unlabelledEssentials Platelets employ proteins/signaling pathways traditionally thought reserved for nuclear niche. We determined retinoic-acid-receptor alpha (RARα) expression and function in human platelets. RARα/actin-related protein-2/3 complex (Arp2/3) interact via non-genomic signaling in platelets. RARα regulates Arp2/3-mediated actin cytoskeletal dynamics and platelet spreading. SUMMARY: Background Platelets utilize proteins and pathways classically reserved for the nuclear niche. Methods We determined whether human platelets express retinoic-acid-receptor family members, traditionally thought of as nuclear transcription factors, and deciphered the function of RARα. Results We found that RARα is robustly expressed in human platelets and megakaryocytes and interacts directly with actin-related protein-2/3 complex (Arp2/3) subunit 5 (Arp2/3s5). Arp2/3s5 co-localized with RARα in situ and regulated platelet cytoskeletal processes. The RARα ligand all-trans retinoic acid (atRA) disrupted RARα-Arp2/3 interactions. When isolated human platelets were treated with atRA, rapid cytoskeletal events (e.g. platelet spreading) were inhibited. In addition, when platelets were cultured for 18 h in the presence of atRA, actin-dependent morphological changes (e.g. extended cell body formation) were similarly inhibited. Using in vitro actin branching assays, RARα and Arp2/3-regulated complex actin branch formation was demonstrated. Consistent with inhibition of cytoskeletal processes in platelets, atRA, when added to this branching assay, resulted in dysregulated actin branching. Conclusion Our findings identify a previously unknown mechanism by which RARα regulates Arp2/3-mediated actin cytoskeletal dynamics through a non-genomic signaling pathway. These findings have broad implications in both nucleated and anucleate cells, where actin cytoskeletal events regulate cell morphology, movement and division.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.