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Blood May 2022
Topics: Actin Cytoskeleton; Actins; Extracellular Traps; Neutrophils
PubMed: 35616987
DOI: 10.1182/blood.2022015562 -
Molecular Biology of the Cell May 2022Clathrin-mediated endocytosis (CME) robustness under elevated membrane tension is maintained by actin assembly-mediated force generation. However, whether more actin...
Clathrin-mediated endocytosis (CME) robustness under elevated membrane tension is maintained by actin assembly-mediated force generation. However, whether more actin assembles at endocytic sites in response to increased load has not previously been investigated. Here actin network ultrastructure at CME sites was examined under low and high membrane tension. Actin and N-WASP spatial organization indicate that actin polymerization initiates at the base of clathrin-coated pits and that the network then grows away from the plasma membrane. Actin network height at individual CME sites was not coupled to coat shape, raising the possibility that local differences in mechanical load feed back on assembly. By manipulating membrane tension and Arp2/3 complex activity, we tested the hypothesis that actin assembly at CME sites increases in response to elevated load. Indeed, in response to elevated membrane tension, actin grew higher, resulting in greater coverage of the clathrin coat, and CME slowed. When membrane tension was elevated and the Arp2/3 complex was inhibited, shallow clathrin-coated pits accumulated, indicating that this adaptive mechanism is especially crucial for coat curvature generation. We propose that actin assembly increases in response to increased load to ensure CME robustness over a range of plasma membrane tensions.
Topics: Actin-Related Protein 2-3 Complex; Actins; Cell Membrane; Clathrin; Endocytosis
PubMed: 35389747
DOI: 10.1091/mbc.E21-11-0589 -
International Journal of Molecular... Mar 2022Ezrin is one of the members of the ezrin/radixin/moesin (ERM) family of proteins. It was originally discovered as an actin-binding protein in the microvilli structure... (Review)
Review
Ezrin is one of the members of the ezrin/radixin/moesin (ERM) family of proteins. It was originally discovered as an actin-binding protein in the microvilli structure about forty years ago. Since then, it has been revealed as a key protein with functions in a variety of fields including cell migration, survival, and signal transduction, as well as functioning as a structural component. Ezrin acts as a cross-linker of membrane proteins or phospholipids in the plasma membrane and the actin cytoskeleton. It also functions as a platform for signaling molecules at the cell surface. Moreover, ezrin is regarded as an important target protein in cancer diagnosis and therapy because it is a key protein involved in cancer progression and metastasis, and its high expression is linked to poor survival in many cancers. Small molecule inhibitors of ezrin have been developed and investigated as candidate molecules that suppress cancer metastasis. Here, we wish to comprehensively review the roles of ezrin from the pathophysiological points of view.
Topics: Actin Cytoskeleton; Actins; Cell Membrane; Cytoskeletal Proteins; Microfilament Proteins; Phosphoproteins
PubMed: 35328667
DOI: 10.3390/ijms23063246 -
Virulence Dec 2022The soil saprophyte, , is the causative agent of melioidosis, a disease endemic in South East Asia and northern Australia. Exposure to by either inhalation or... (Review)
Review
The soil saprophyte, , is the causative agent of melioidosis, a disease endemic in South East Asia and northern Australia. Exposure to by either inhalation or inoculation can lead to severe disease. rapidly shifts from an environmental organism to an aggressive intracellular pathogen capable of rapidly spreading around the body. The expression of multiple virulence factors at every stage of intracellular infection allows for rapid progression of infection. Following invasion or phagocytosis, resists host-cell killing mechanisms in the phagosome, followed by escape using the type III secretion system. Several secreted virulence factors manipulate the host cell, while bacterial cells undergo a shift in energy metabolism allowing for overwhelming intracellular replication. Polymerisation of host cell actin into "actin tails" propels to the membranes of host cells where the type VI secretion system fuses host cells into multinucleated giant cells (MNGCs) to facilitate cell-to-cell dissemination. This review describes the various mechanisms used by to survive within cells.
Topics: Humans; Burkholderia pseudomallei; Virulence; Actins; Melioidosis; Virulence Factors
PubMed: 36271712
DOI: 10.1080/21505594.2022.2139063 -
Molecular Biology of the Cell Aug 2022Cytoplasmic β- and γ-actin proteins are 99% identical but support unique organismal functions. The cytoplasmic actin nucleotide sequences and , respectively, are...
Cytoplasmic β- and γ-actin proteins are 99% identical but support unique organismal functions. The cytoplasmic actin nucleotide sequences and , respectively, are more divergent but still 89% similar. mice are embryonic lethal and cells fail to proliferate, but editing the gene to express γ-actin () resulted in none of the overt phenotypes of the knockout revealing protein-independent functions for . To determine if has a protein-independent function, we crossed and mice to generate the bG/0 line, where the only cytoplasmic actin expressed is γ-actin from . The bG/0 mice were viable but showed a survival defect despite expressing γ-actin protein at levels no different from bG/gG with normal survival. A unique myopathy phenotype was also observed in bG/0 mice. We conclude that impaired survival and myopathy in bG/0 mice are due to loss of nucleotide-dependent function(s). On the other hand, the bG/0 genotype rescued functions impaired by , including cell proliferation and auditory function, suggesting a role for γ-actin protein in both fibroblasts and hearing. Together, these results identify nucleotide-dependent functions for while implicating γ-actin protein in more cell-/tissue-specific functions.
Topics: Animals; Mice; Actins; Cytoplasm; Fibroblasts; Nucleotides; Phenotype
PubMed: 35594181
DOI: 10.1091/mbc.E22-02-0054 -
ELife Dec 2023The conformational state of a structural protein in bacteria can vary, depending on the concentration level of potassium ions or the nucleotide bound to it.
The conformational state of a structural protein in bacteria can vary, depending on the concentration level of potassium ions or the nucleotide bound to it.
Topics: Actins; Bacterial Proteins; Nucleotides; Bacteria
PubMed: 38088194
DOI: 10.7554/eLife.93719 -
The FEBS Journal Oct 2022Invadosomes are protrusive and mechanosensitive actin devices critical for cell migration, invasion, and extracellular matrix remodeling. The dynamic, proteolytic, and... (Review)
Review
Invadosomes are protrusive and mechanosensitive actin devices critical for cell migration, invasion, and extracellular matrix remodeling. The dynamic, proteolytic, and protrusive natures of invadosomes have made these structures fascinating and attracted many scientists to develop new technologies for their analysis. With these exciting methodologies, many biochemical and biophysical properties of invadosomes have been well characterized and appreciated, and those discoveries elegantly explained the biological and pathological effects of invadosomes in human health and diseases. In this review, we focus on these commonly used or newly developed methods for invadosome analysis and effort to reason some discrepancies among those assays. Finally, we explore the opposite regulatory mechanisms among invadosomes and focal adhesions, another actin-rich adhesive structures, and speculate a potential rule for their switch.
Topics: Actins; Cell Movement; Extracellular Matrix; Humans; Podosomes; Proteolysis
PubMed: 34196119
DOI: 10.1111/febs.16098 -
Molecular Biology of the Cell Nov 2023Many eukaryotic cells, including animal cells and unicellular amoebae, use dynamic-actin networks to crawl across solid surfaces. Recent discoveries of actin-dependent... (Review)
Review
Many eukaryotic cells, including animal cells and unicellular amoebae, use dynamic-actin networks to crawl across solid surfaces. Recent discoveries of actin-dependent crawling in additional lineages have sparked interest in understanding how and when this type of motility evolved. Tracing the evolution of cell crawling requires understanding the molecular mechanisms underlying motility. Here we outline what is known about the diversity and evolution of the molecular mechanisms that drive cell motility, with a focus on actin-dependent crawling. Classic studies and recent work have revealed a surprising number of distinct mechanical modes of actin-dependent crawling used by different cell types and species to navigate different environments. The overlap in actin network regulators driving multiple types of actin-dependent crawling, along with cortical-actin networks that support the plasma membrane in these cells, suggest that actin motility and cortical actin networks might have a common evolutionary origin. The rapid development of additional evolutionarily diverse model systems, advanced imaging technologies, and CRISPR-based genetic tools, is opening the door to testing these and other new ideas about the evolution of actin-dependent cell crawling.
Topics: Animals; Actins; Cell Movement; Cell Membrane
PubMed: 37906436
DOI: 10.1091/mbc.E22-08-0358 -
ELife Nov 2023The MRTF-SRF pathway has been extensively studied for its crucial role in driving the expression of a large number of genes involved in actin cytoskeleton of various...
The MRTF-SRF pathway has been extensively studied for its crucial role in driving the expression of a large number of genes involved in actin cytoskeleton of various cell types. However, the specific contribution of MRTF-SRF in hair cells remains unknown. In this study, we showed that hair cell-specific deletion of or , but not a, leads to similar defects in the development of stereocilia dimensions and the maintenance of cuticular plate integrity. We used fluorescence-activated cell sorting-based hair cell RNA-Seq analysis to investigate the mechanistic underpinnings of the changes observed in and mutants, respectively. Interestingly, the transcriptome analysis revealed distinct profiles of genes regulated by and , suggesting different transcriptional regulation mechanisms of actin cytoskeleton activities mediated by and . Exogenous delivery of calponin 2 using Adeno-associated virus transduction in mutants partially rescued the impairments of stereocilia dimensions and the F-actin intensity of cuticular plate, suggesting the involvement of , as an downstream target, in regulating the hair bundle morphology and cuticular plate actin cytoskeleton organization. Our study uncovers, for the first time, the unexpected differential transcriptional regulation of actin cytoskeleton mediated by and in hair cells, and also demonstrates the critical role of SRF-CNN2 in modulating actin dynamics of the stereocilia and cuticular plate, providing new insights into the molecular mechanism underlying hair cell development and maintenance.
Topics: Hair Cells, Auditory; Actin Cytoskeleton; Stereocilia; Actins; Gene Expression Regulation
PubMed: 37982489
DOI: 10.7554/eLife.90155 -
Cytoskeleton (Hoboken, N.J.) Jun 2021The actin cytoskeleton is important for maintaining mechanical homeostasis in adherent cells, largely through its regulation of adhesion and cortical tension. The LIM... (Review)
Review
The actin cytoskeleton is important for maintaining mechanical homeostasis in adherent cells, largely through its regulation of adhesion and cortical tension. The LIM (Lin-11, Isl1, MEC-3) domain-containing proteins are involved in a myriad of cellular mechanosensitive pathways. Recent work has discovered that LIM domains bind to mechanically stressed actin filaments, suggesting a novel and widely conserved mechanism of mechanosensing. This review summarizes the current state of knowledge of LIM protein mechanosensitivity.
Topics: Actin Cytoskeleton; Actins; Biophysics; Cell Communication; LIM Domain Proteins; Protein Binding
PubMed: 34028199
DOI: 10.1002/cm.21677