β-actin function in platelets and red blood cells can be performed by γ-actin and is therefore independent of actin isoform protein sequence
Actin is an essential component of the cytoskeleton in every eukaryotic cell. β-and γ-nonmuscle actin are over 99% identical to each other at the protein level but are encoded by different genes and play distinct roles in vivo. Blood cells, especially red blood cells (RBC), contain almost exclusively β-actin, and it has been generally assumed that this bias is dictated by the unique suitability of β-actin for RBC cytoskeleton function due to its specific amino acid sequence. Here we tested this assumption by analyzing the "β-coded γ-actin" (Actbcg) mouse model, in which the β-actin gene is edited by five-point mutations to produce γ-actin protein. Strikingly, despite lacking β-actin protein, Actbcg mice had no detectable phenotypes in RBCs, and no changes in the RBC shape, integrity, deformability, and molecular composition of their spectrin-based membrane skeleton. No actin-dependent changes were observed in platelets, another anucleate cell type enriched for β-actin. Our data show that, contrary to expectations, β-actin function in mature RBCs and platelets is independent of its protein sequence and therefore its enrichment in hematopoiesis and mature blood cells is likely driven entirely by its nucleotide-dependent functions.
Authors
- Devasmita Chakravarty
- Rustem I. Litvinov (ORCID: https://orcid.org/0000-0003-0643-1496)
- Mark N. Levine (ORCID: https://orcid.org/0000-0003-1288-0773)
- Kartick Patra (ORCID: https://orcid.org/0000-0002-5636-7739)
- Enrico Radaelli (ORCID: https://orcid.org/0000-0002-2885-0221)
- Aae Suzuki (ORCID: https://orcid.org/0009-0002-4569-6972)
- Megan Coffin (ORCID: https://orcid.org/0000-0003-0223-8170)
- Charles S. Abrams (ORCID: https://orcid.org/0009-0000-6973-6137)
- Velia M. Fowler (ORCID: https://orcid.org/0000-0002-3161-8802)
- Alina D. Peshkova (ORCID: https://orcid.org/0000-0002-8790-1818)
- Anna Kashina (ORCID: https://orcid.org/0000-0002-0243-6866)
- Pavan Vedula (ORCID: https://orcid.org/0000-0002-9914-0008)
- Charles‐Antoine Assenmacher (ORCID: https://orcid.org/0000-0003-0073-2730)
- Li Chen (ORCID: https://orcid.org/0000-0003-1939-9659)
- Liang Zhao (ORCID: https://orcid.org/0009-0004-5999-8976)
- Stephanie Sterling (ORCID: https://orcid.org/0000-0003-1521-0126)
Institutions
- National Institutes of Health (US)
- National Institute of Diabetes and Digestive and Kidney Diseases (US)
- University of Pennsylvania (US)
- University of Delaware (US)
Publication Details
- Journal
- Molecular Biology of the Cell
- Published
- 2024-12-20
- DOI
- https://doi.org/10.1091/mbc.e24-04-0186
- Citations
- 1
- Primary Topic
- Blood properties and coagulation
- Type
- article
- Field-Weighted Citation Impact
- 0.42
Funders
- University of Pennsylvania
- Delaware IDeA Network of Biomedical Research Excellence
- National Institutes of Health
- National Institute of General Medical Sciences