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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 -
Seminars in Cell Biology Jun 1994The recent elucidation of the three-dimensional structure of gelsolin segment 1 and profilin provides new insights on how these proteins recognize actin. Although the... (Review)
Review
The recent elucidation of the three-dimensional structure of gelsolin segment 1 and profilin provides new insights on how these proteins recognize actin. Although the picture is still incomplete and not all biochemical data are consolidated, the results offer clues on how these proteins exert their effect on actin and how they may modulate the cytoskeleton dynamics. Binding studies on the villin head piece, thymosin beta 4 and mutants of both peptides allowed to identify critical residues important for actin binding and give the first picture of new actin binding interfaces. The interface of the modelled actomyosin complex is also briefly discussed.
Topics: Actins; Amino Acid Sequence; Animals; Binding Sites; Cell Movement; Humans; Microfilament Proteins; Molecular Sequence Data; Protein Conformation
PubMed: 7919231
DOI: 10.1006/scel.1994.1022 -
Cell Communication and Signaling : CCS Jun 2018TRIO and F-actin-binding protein (TRIOBP) also referred to as Tara, was originally isolated as a cytoskeleton remodeling protein. TRIOBP-1 is important for regulating... (Review)
Review
TRIO and F-actin-binding protein (TRIOBP) also referred to as Tara, was originally isolated as a cytoskeleton remodeling protein. TRIOBP-1 is important for regulating F-actin filament reorganization. TRIOBP variants are broadly classified as variant-1 or - 4 and do not share exons. TRIOBP variant-5 contains all exons. Earlier studies indicated that TRIOBP-4/5 mutation is a pivotal element of autosomal recessive nonsyndromic hearing loss. However, recent studies provide clues that TRIOBP variants are associated with other human diseases including cancer and brain diseases. In this review, recent functional studies focusing on TRIOBP variants and its possible disease models are described.
Topics: Brain; Disease; Genetic Variation; Hearing Loss; Humans; Microfilament Proteins; Neoplasms
PubMed: 29890989
DOI: 10.1186/s12964-018-0237-y -
Cytoskeleton (Hoboken, N.J.) May 2021Through the process of chemotactic migration, neutrophils are able to recruit to an inflammatory site and eliminate pathogens, thus playing a vital role in host defense....
Through the process of chemotactic migration, neutrophils are able to recruit to an inflammatory site and eliminate pathogens, thus playing a vital role in host defense. The process of neutrophil chemotaxis is mediated by dynamic actin reorganization and polymerization. Adseverin, an actin-binding protein and member of the Gelsolin superfamily of proteins, has been hypothesized to regulate goal directed movement through the capping and severing of actin filaments, but has never been investigated in the context of neutrophil chemotaxis. Using an Adseverin knockout mouse model, we show that Adseverin plays a role in subcortical F-actin assembly at the leading edge during chemotaxis through the generation of free barbed ends on existing actin filaments. In addition, in the absence of Adseverin, neutrophils show reduced speed of migration in vitro and in vivo. This study indicates that Adseverin is a regulator of actin filament generation during neutrophil chemotaxis.
Topics: Actins; Animals; Gelsolin; Mice; Microfilament Proteins; Neutrophils
PubMed: 34370397
DOI: 10.1002/cm.21684 -
Expert Reviews in Molecular Medicine Jan 2019Gelsolin (GSN), one of the most abundant actin-binding proteins, is involved in cell motility, shape and metabolism. As a member of the GSN superfamily, GSN is a highly... (Review)
Review
Gelsolin (GSN), one of the most abundant actin-binding proteins, is involved in cell motility, shape and metabolism. As a member of the GSN superfamily, GSN is a highly structured protein in eukaryotic cells that can be regulated by calcium concentration, intracellular pH, temperature and phosphatidylinositol-4,5-bisphosphate. GSN plays an important role in cellular mechanisms as well as in different cellular interactions. Because of its participation in immunologic processes and its interaction with different cells of the immune system, GSN is a potential candidate for various therapeutic applications. In this review, we summarise the structure of GSN as well as its regulating and functional roles, focusing on distinct diseases such as Alzheimer's disease, rheumatoid arthritis and cancer. A short overview of GSN as a therapeutic target in today's medicine is also provided.
Topics: Animals; Biomarkers; Cell Communication; Disease Susceptibility; Gelsolin; Gene Expression Regulation; Humans; Microfilament Proteins; Molecular Targeted Therapy; Signal Transduction; Structure-Activity Relationship
PubMed: 30698126
DOI: 10.1017/erm.2018.7 -
Journal of Tissue Engineering and... Aug 2019Chondrocytes dedifferentiate as a result of monolayer culture for cell number expansion. This is associated with the development of an elongated shape, increased actin...
Chondrocytes dedifferentiate as a result of monolayer culture for cell number expansion. This is associated with the development of an elongated shape, increased actin polymerization, development of stress fibres, and expression of contractile molecules. Given the changes in actin status with dedifferentiation, the hypothesis of this study was that adseverin, an actin severing and capping protein, plays a role in regulating chondrocyte phenotype and function. This study reports that serial passaging of articular chondrocytes in monolayer culture resulted in loss of adseverin protein expression as early as Day 14 of culture and remained repressed in Passage 2 (P2) cells. Knockdown of adseverin by siRNA in primary chondrocytes promoted an increase in cell size and an elongated shape, actin stress fibres, decreased G-/F-actin ratio, and increased number of actin-free barbed ends. The cells also showed increased expression of the contractile genes and proteins, vinculin and α-smooth muscle actin, and increased ability to contract collagen gels. These are all features of dedifferentiation. These effects were due to adseverin as adseverin overexpression following transfection of the green fluorescent protein-adseverin plasmid partially reversed all of these changes in P2 chondrocytes. Furthermore, sox9 and aggrecan chondrogenic gene expression was upregulated, and collagen type I genes expression was downregulated with adseverin overexpression. The change in aggrecan mRNA expression had functional consequence as these cells exhibited increased total proteoglycan synthesis. These findings demonstrate that adseverin regulates features indicative of redifferentiation in passaged articular chondrocytes through modulation of the actin cytoskeleton status and potentially may regulate the maintenance of phenotype in primary chondrocytes.
Topics: Animals; Cartilage, Articular; Cattle; Cell Differentiation; Cell Shape; Cell Size; Chondrocytes; Chondrogenesis; Gelsolin; Gene Expression Regulation; Microfilament Proteins; Phenotype; Polymerization; Rats
PubMed: 31090208
DOI: 10.1002/term.2898 -
Trends in Cell Biology Feb 2018Cortactin fulfills many functions in various cell types. These functions have been considered to derive from its ability to activate the Actin-related protein 2/3... (Review)
Review
Cortactin fulfills many functions in various cell types. These functions have been considered to derive from its ability to activate the Actin-related protein 2/3 (Arp2/3) complex, and are regulated by post-translational modifications, including phosphorylation and acetylation. New evidence suggests that cortactin regulates cell migration by controlling the deposition of extracellular matrix proteins rather than lamellipodial Arp2/3 activation, and that cortactin also functions in GTPase signaling, vesicular trafficking, and actomyosin contractility. These recent new findings and concepts are relevant for physiological and pathological cell functions, but have not yet been put into mechanistic context. Here, we reconsider current thinking on cortactin functions in different cell types during health and disease, and discuss potential directions of future research in cortactin biology.
Topics: Actins; Amino Acid Sequence; Animals; Cortactin; Humans; Microfilament Proteins; Protein Binding; Signal Transduction
PubMed: 29162307
DOI: 10.1016/j.tcb.2017.10.009 -
Annual Review of Biophysics and... 1995This review describes three structures of actin complexed with different monomer-binding proteins, namely with DNase I, gelsolin segment 1, and profilin. In these... (Review)
Review
This review describes three structures of actin complexed with different monomer-binding proteins, namely with DNase I, gelsolin segment 1, and profilin. In these proteins, the binding sites are discontinuous in the sequence, and those residues that form intermolecular hydrogen bonds are not well conserved in homologous proteins. The strongly conserved residues that define the family of proteins in gelsolin and profilin reflect the underlying structural fold of each. The binding surfaces for segment 1 and profilin are different, although they peripherally overlap on actin. No extreme features in the binding surfaces of these complexes distinguish them from other globular proteins.
Topics: Actins; Amino Acid Sequence; Binding Sites; Contractile Proteins; Deoxyribonuclease I; Gelsolin; Microfilament Proteins; Molecular Sequence Data; Profilins; Protein Binding; Protein Conformation
PubMed: 7663130
DOI: 10.1146/annurev.bb.24.060195.003235 -
Trends in Cell Biology Apr 2011The transmittance of force from the actin cytoskeleton via integrins to extracellular ligands is essential for multiple aspects of leukocyte function. In addition,... (Review)
Review
The transmittance of force from the actin cytoskeleton via integrins to extracellular ligands is essential for multiple aspects of leukocyte function. In addition, integrins must be efficiently linked to the cytoskeleton in order to resist external forces that act on the cell. Recently, the mammalian actin-binding protein 1 (mAbp1) was identified as a novel adaptor involved in linking adhesion molecules of the β(2) integrin family to the actin cytoskeleton, indicating that this protein might have a fundamental impact on leukocyte functions that are associated explicitly with force transmittance; namely, intraluminal adhesion and phagocytosis. Here, we review the current understanding of the molecular and cellular functions of mAbp1 with a focus on its impact in leukocyte biology.
Topics: Animals; Cell Adhesion; Cell Movement; Humans; Leukocytes; Microfilament Proteins; Protein Binding
PubMed: 21232959
DOI: 10.1016/j.tcb.2010.12.001 -
The International Journal of... Mar 2009Transgelin is a shape change sensitive 22 kDa actin-binding protein of the calponin family. It contains a C-terminal calponin-like module (CLIK(23)) and an upstream... (Review)
Review
Transgelin is a shape change sensitive 22 kDa actin-binding protein of the calponin family. It contains a C-terminal calponin-like module (CLIK(23)) and an upstream positively charged amino acid region required for actin binding. Transgelin is ubiquitous to vascular and visceral smooth muscle and is an early marker of smooth muscle differentiation, where its expression is driven by CArG box, smooth muscle gene promoter. It is also present in fibroblasts, and some epithelium where expression is likely driven by TGF-beta1. Transgelin null mice reveal that, whilst it is not required for smooth muscle development, transgelin may be involved in calcium-independent smooth muscle contraction. Recent evidence suggests that transgelin acts as a tumour suppressor. Its expression is lost in prostate, breast and colon cancers. This is consistent with suppression of the metallo matrix protease-9 (MMP-9) by transgelin, where MMP-9 is upregulated in these common cancers.
Topics: Animals; Cell Differentiation; Cytoskeleton; Fibroblasts; Humans; Matrix Metalloproteinase 9; Mice; Microfilament Proteins; Muscle Contraction; Muscle Proteins; Myocytes, Smooth Muscle; Neoplasms; Transforming Growth Factor beta1; Tumor Suppressor Proteins
PubMed: 18378184
DOI: 10.1016/j.biocel.2008.02.011