ArticleJournal of immunology (Baltimore, Md. : 1950)2015
UNC-45A Is a Nonmuscle Myosin IIA Chaperone Required for NK Cell Cytotoxicity via Control of Lytic Granule Secretion.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 34 citations in OpenAlex.
- Distinct impacts of human co-chaperone UNC45 paralogs on Drosophila muscle development and function.Journal of cell science · 2025Article
- PM2.5 Induces Cell-Specific Transcriptomic Alterations in the Lungs of Juvenile Mice.Journal of inflammation research · 2025Article
- Engine breakdown of lysosomes and related organelles and the resulting physiology.Frontiers in cell and developmental biology · 2025Review
- Review
- Longitudinal proteomic investigation of COVID-19 vaccination.Protein & cell · 2023Article
- The Actin Regulators Involved in the Function and Related Diseases of Lymphocytes.Frontiers in immunology · 2022Review
- Locked and Loaded: Mechanisms Regulating Natural Killer Cell Lytic Granule Biogenesis and Release.Frontiers in immunology · 2022Review
- Ginsenoside Rg1 ameliorates blood-brain barrier disruption and traumatic brain injuryActa pharmaceutica Sinica. B · 2021Article
- Article
- UNC-45A breaks the microtubule lattice independently of its effects on non-muscle myosin II.Journal of cell science · 2021Article
- The Role of the Cytoskeleton in Regulating the Natural Killer Cell Immune Response in Health and Disease: From Signaling Dynamics to Function.Frontiers in cell and developmental biology · 2021Review
- Mechanosensation and Mechanotransduction in Natural Killer Cells.Frontiers in immunology · 2021Review
- Actin and Myosin in Non-Neuronal Exocytosis.Cells · 2020Review
- Molecular regulation of the plasma membrane-proximal cellular steps involved in NK cell cytolytic function.Journal of cell science · 2020Review
- Actin Cytoskeleton Straddling the Immunological Synapse between Cytotoxic Lymphocytes and Cancer Cells.Cells · 2019Review
- The co-chaperone UNC45A is essential for the expression of mitotic kinase NEK7 and tumorigenesis.The Journal of biological chemistry · 2019Article
- UNC-45A Is a Novel Microtubule-Associated Protein and Regulator of Paclitaxel Sensitivity in Ovarian Cancer Cells.Molecular cancer research : MCR · 2019Article
- UNC-45A is preferentially expressed in epithelial cells and binds to and co-localizes with interphase MTs.Cancer biology & therapy · 2019Article
- Epigenomic signature of adrenoleukodystrophy predicts compromised oligodendrocyte differentiation.Brain pathology (Zurich, Switzerland) · 2018Article
- Loss-of-Function Mutations in UNC45A Cause a Syndrome Associating Cholestasis, Diarrhea, Impaired Hearing, and Bone Fragility.American journal of human genetics · 2018Article
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Authors and funding
13 authors at 5 institutions in 2 countries.
Funding
Abstract
NK cell's killing is a tightly regulated process under the control of specific cytoskeletal proteins. This includes Wiskott-Aldrich syndrome protein, Wiskott-Aldrich syndrome protein-interacting protein, cofilin, Munc13-4, and nonmuscle myosin IIA (NMIIA). These proteins play a key role in controlling NK-mediated cytotoxicity either via regulating the attachment of lytic granules to the actin-based cytoskeleton or via promoting the cytoskeletal reorganization that is requisite for lytic granule release. UNC-45A is a highly conserved member of the UNC-45/CRO1/She4p family of proteins that act as chaperones for both conventional and nonconventional myosin. Although we and others have shown that in lower organisms and in mammalian cells NMIIA-associated functions, such as cytokinesis, cell motility, and organelle trafficking, are dependent upon the presence of UNC-45A, its role in NK-mediated functions is largely unknown. In this article, we describe UNC-45A as a key regulator of NK-mediated cell toxicity. Specifically we show that, in human NK cells, UNC-45A localize at the NK cell immunological synapse of activated NK cells and is part of the multiprotein complex formed during NK cell activation. Furthermore, we show that UNC-45A is disposable for NK cell immunological synapse formation and lytic granules reorientation but crucial for lytic granule exocytosis. Lastly, loss of UNC-45A leads to reduced NMIIA binding to actin, suggesting that UNC-45A is a crucial component in regulating human NK cell cytoskeletal dynamics via promoting the formation of actomyosin complexes.
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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.