Non-genomic activities of retinoic acid receptor alpha control actin cytoskeletal events in human platelets.
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ABSTRACT: Essentials Platelets employ proteins/signaling pathways traditionally thought reserved for nuclear niche. We determined retinoic-acid-receptor alpha (RAR?) expression and function in human platelets. RAR?/actin-related protein-2/3 complex (Arp2/3) interact via non-genomic signaling in platelets. RAR? regulates Arp2/3-mediated actin cytoskeletal dynamics and platelet spreading.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 RAR?. Results We found that RAR? 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 RAR? in situ and regulated platelet cytoskeletal processes. The RAR? ligand all-trans retinoic acid (atRA) disrupted RAR?-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, RAR? 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 RAR? 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.
SUBMITTER: Rondina MT
PROVIDER: S-EPMC5497578 | biostudies-literature | 2016 May
REPOSITORIES: biostudies-literature
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