ArticleBlood2015
Immunodeficiency and severe susceptibility to bacterial infection associated with a loss-of-function homozygous mutation of MKL1.
Article in Blood, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 83 citations in OpenAlex.
- Comprehensive analysis of regulated cell death pathways: intrinsic disorder, protein-protein interactions, and cross-pathway communication.Apoptosis : an international journal on programmed cell death · 2025Pooled it
- Antiviral cellular therapy for enhancing T-cell reconstitution before or after hematopoietic stem cell transplantation (ACES): a two-arm, open label phase II interventional trial of pediatric patients with risk factor assessment.Nature communications · 2024Trial
- Prevalence and Functional Roles of Intrinsic Disorder in the [F-actin]-monooxygenase MICAL Family Members and their Interactors.Cell biochemistry and biophysics · 2026Article
- RPSA-OLFM4 axis governs neutrophil migration against bacterial infection and sepsis.Nature communications · 2026Article
- Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation.Nature reviews. Immunology · 2026Review
- LIMK1 variants are associated with divergent endocrinological phenotypes and altered exocytosis dynamics.iScience · 2025Article
- Focus on mechano-immunology: new direction in cancer treatment.International journal of surgery (London, England) · 2025Review
- mDia2 is an important mediator of MRTF-A-dependent regulation of breast cancer cell migration.Molecular biology of the cell · 2024Article
- IL-2 delivery to CD8Nature communications · 2024Article
- Cardiac biopsies reveal differences in transcriptomics between left and right ventricle in patients with or without diagnostic signs of heart failure.Scientific reports · 2024Article
- Inhibition of MRTF activation as a clinically achievable anti-fibrotic mechanism for pirfenidone.The European respiratory journal · 2023Article
- Tuning immunity through tissue mechanotransduction.Nature reviews. Immunology · 2023Review
- First Successful Allogeneic Hematopoietic Stem Cell Transplantation for MKL1 Deficiency.Journal of clinical immunology · 2022Article
- Expression of the phagocytic receptors αFrontiers in immunology · 2022Article
- Research progress in myosin light chain 9 in malignant tumors.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2021Article
- Molecular Mechanisms of Leukocyte Migration and Its Potential Targeting-Lessons Learned From MKL1/SRF-Related Primary Immunodeficiency Diseases.Frontiers in immunology · 2021Review
- When Actin is Not Actin' Like It Should: A New Category of Distinct Primary Immunodeficiency Disorders.Journal of innate immunity · 2021Review
- Actin Dynamics at the T Cell Synapse as Revealed by Immune-Related Actinopathies.Frontiers in cell and developmental biology · 2021Review
- Journey to the Center of the Cell: Cytoplasmic and Nuclear Actin in Immune Cell Functions.Frontiers in cell and developmental biology · 2021Review
- Molecular Tuning of Actin Dynamics in Leukocyte Migration as Revealed by Immune-Related Actinopathies.Frontiers in immunology · 2021Review
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Megakaryoblastic leukemia 1 (MKL1), also known as MAL or myocardin-related transcription factor A (MRTF-A), is a coactivator of serum response factor, which regulates transcription of actin and actin cytoskeleton-related genes. MKL1 is known to be important for megakaryocyte differentiation and function in mice, but its role in immune cells is unexplored. Here we report a patient with a homozygous nonsense mutation in the MKL1 gene resulting in immunodeficiency characterized predominantly by susceptibility to severe bacterial infection. We show that loss of MKL1 protein expression causes a dramatic loss of filamentous actin (F-actin) content in lymphoid and myeloid lineage immune cells and widespread cytoskeletal dysfunction. MKL1-deficient neutrophils displayed reduced phagocytosis and almost complete abrogation of migration in vitro. Similarly, primary dendritic cells were unable to spread normally or to form podosomes. Silencing of MKL1 in myeloid cell lines revealed that F-actin assembly was abrogated through reduction of globular actin (G-actin) levels and disturbed expression of multiple actin-regulating genes. Impaired migration of these cells was associated with failure of uropod retraction likely due to altered contractility and adhesion, evidenced by reduced expression of the myosin light chain 9 (MYL9) component of myosin II complex and overexpression of CD11b integrin. Together, our results show that MKL1 is a nonredundant regulator of cytoskeleton-associated functions in immune cells and fibroblasts and that its depletion underlies a novel human primary immunodeficiency.
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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.