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Science Advances Aug 2023In osteoarthritis (OA), a disease characterized by progressive articular cartilage degradation and calcification, the articular chondrocyte phenotype changes and this...
In osteoarthritis (OA), a disease characterized by progressive articular cartilage degradation and calcification, the articular chondrocyte phenotype changes and this correlates with actin cytoskeleton alterations suggesting that it regulates gene expression essential for proper phenotype. This study reports that OA is associated with the loss of adseverin, an actin capping and severing protein. Adseverin deletion (Adseverin) in mice compromised articular chondrocyte function, by reducing F-actin and aggrecan expression and increasing apoptosis, Indian hedgehog, Runx2, MMP13, and collagen type X expression, and cell proliferation. This led to stiffer cartilage and decreased hyaline and increased calcified cartilage thickness. Together, these changes predisposed the articular cartilage to enhanced OA severity in Adseverin mice who underwent surgical induction of OA. Adseverin chondrocyte RNA sequencing and in vitro studies together suggests that adseverin modulates cell viability and prevents mineralization. Thus, adseverin maintains articular chondrocyte phenotype and cartilage tissue homeostasis by preventing progression to hypertrophic differentiation in vivo. Adseverin may be chondroprotective and a potential therapeutic target.
Topics: Mice; Animals; Microfilament Proteins; Chondrocytes; Hedgehog Proteins; Osteoarthritis; Cell Differentiation; Cartilage, Articular; Actins
PubMed: 37540756
DOI: 10.1126/sciadv.adf1130 -
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 -
Developmental Dynamics : An Official... Nov 2021Lens morphogenesis, architecture, and clarity are known to be critically dependent on actin cytoskeleton organization and cell adhesive interactions. There is limited...
BACKGROUND
Lens morphogenesis, architecture, and clarity are known to be critically dependent on actin cytoskeleton organization and cell adhesive interactions. There is limited knowledge, however regarding the identity and role of key proteins regulating actin cytoskeletal organization in the lens. This study investigated the role of drebrin, a developmentally regulated actin-binding protein, in mouse lens development by generating and characterizing a conditional knockout (cKO) mouse model using the Cre-LoxP recombination approach.
RESULTS
Drebrin E, a splice variant of DBN1 is a predominant isoform expressed in the mouse lens and exhibits a maturation-dependent downregulation. Drebrin co-distributes with actin in both epithelium and fibers. Conditional deficiency (both haploinsufficiency and complete absence) of drebrin results in disrupted lens morphogenesis leading to cataract and microphthalmia. The drebrin cKO lens reveals a dramatic decrease in epithelial height and width, E-cadherin, and proliferation, and increased apoptotic cell death and expression of α-smooth muscle actin, together with severely impaired fiber cell organization, polarity, and cell-cell adhesion.
CONCLUSIONS
This study demonstrates the requirement of drebrin in lens development and growth, with drebrin deficiency leading to impaired lens morphogenesis and microphthalmia.
Topics: Actins; Animals; Cell Communication; Lens, Crystalline; Mice; Microfilament Proteins; Morphogenesis
PubMed: 33896079
DOI: 10.1002/dvdy.353 -
Discovery Medicine 2021Actin-binding protein (transgelin, TAGLN) is a kind of protein that regulates actin polymerization, aggregating (or bundling), or cross-linking. As a member of the... (Review)
Review
Actin-binding protein (transgelin, TAGLN) is a kind of protein that regulates actin polymerization, aggregating (or bundling), or cross-linking. As a member of the actin-binding protein complex, transgelin-2 is involved in the regulation of cytoskeleton. Transgelin-2 is widely expressed in various tissues and organs of the body, but its abnormal expression is often seen in all kinds of tumors, which is related to the occurrence and development, and especially the invasion, metastasis, and drug resistance in many kinds of malignant tumors. However, the signal pathway involved in the regulation of transgelin-2 and its mechanism have remained to be elucidated. In recent years, with a more in-depth study of transgelin-2, its relationship with tumorigenesis has become increasingly clear. Therefore, we review recent research progress in transgelin-2, which is helpful to provide ideas for further research and bring forth a new scheme for the diagnosis, treatment, and prognosis of tumors.
Topics: Carcinogenesis; Humans; Microfilament Proteins; Muscle Proteins; Neoplasms
PubMed: 35219353
DOI: No ID Found -
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 -
International Journal of Molecular... Oct 2023The involvement of the actin-regulatory protein, gelsolin (GSN), in neoplastic transformation has been reported in different cancers including bladder cancer. However,...
The involvement of the actin-regulatory protein, gelsolin (GSN), in neoplastic transformation has been reported in different cancers including bladder cancer. However, the exact mechanism by which GSN influences bladder cancer development is not well understood. Here, we sought to reveal the functional significance of GSN in bladder cancer by undertaking a comprehensive bioinformatic analysis of TCGA datasets and through the assessment of multiple biological functions. GSN expression was knocked down in bladder cancer cell lines with two siRNA isoforms targeting GSN. Proliferation, migration, cell cycle and apoptosis assays were carried out. GSN expression, enrichment analysis, protein-protein interaction and immune infiltration analysis were verified through online TCGA tools. The data indicated that GSN expression is associated with bladder cancer proliferation, migration and enhanced cell apoptosis through regulation of NF-κB expression. GSN expression correlated with various inflammatory cells and may influence the immunity of the tumor microenvironment. Computational analysis identified several interacting partners which are associated with cancer progression and patient outcome. The present results demonstrate that GSN plays an important role in bladder cancer pathogenesis and may serve as a potential biomarker and therapeutic target for cancer therapy.
Topics: Humans; Microfilament Proteins; Gelsolin; Urinary Bladder; Urinary Bladder Neoplasms; Carcinoma; Tumor Microenvironment
PubMed: 37958747
DOI: 10.3390/ijms242115763 -
Mammalian Actin-binding Protein-1/Hip-55 Interacts with FHL2 and Negatively Regulates Cell Invasion.The Journal of Biological Chemistry Jul 2016Mammalian actin-binding protein-1 (mAbp1) is an adaptor protein that binds actin and modulates scission during endocytosis. Recent studies suggest that mAbp1 impairs...
Mammalian actin-binding protein-1 (mAbp1) is an adaptor protein that binds actin and modulates scission during endocytosis. Recent studies suggest that mAbp1 impairs cell invasion; however, the mechanism for the inhibitory effects of mAbp1 remain unclear. We performed a yeast two-hybrid screen and identified the adaptor protein, FHL2, as a novel binding partner that interacts with the N-terminal actin depolymerizing factor homology domain (ADFH) domain of mAbp1. Here we report that depletion of mAbp1 or ectopic expression of the ADFH domain of mAbp1 increased Rho GTPase signaling and breast cancer cell invasion. Moreover, cell invasion induced by the ADFH domain of mAbp1 required the expression of FHL2. Taken together, our findings show that mAbp1 and FHL2 are novel binding partners that differentially regulate Rho GTPase signaling and MTLn3 breast cancer cell invasion.
Topics: Animals; Breast Neoplasms; Cell Line, Tumor; Humans; LIM-Homeodomain Proteins; Microfilament Proteins; Muscle Proteins; Neoplasm Invasiveness; Rats; Transcription Factors; Two-Hybrid System Techniques; src Homology Domains
PubMed: 27129278
DOI: 10.1074/jbc.M116.725739 -
Histochemistry and Cell Biology Apr 2016Extensive research in the past decade has significantly broadened our view about the role actin plays in the life of the cell and added novel aspects to actin research.... (Review)
Review
Extensive research in the past decade has significantly broadened our view about the role actin plays in the life of the cell and added novel aspects to actin research. One of these new aspects is the discovery of the existence of nuclear actin which became evident only recently. Nuclear activities including transcriptional activation in the case of all three RNA polymerases, editing and nuclear export of mRNAs, and chromatin remodeling all depend on actin. It also became clear that there is a fine-tuned equilibrium between cytoplasmic and nuclear actin pools and that this balance is ensured by an export-import system dedicated to actin. After over half a century of research on conventional actin and its organizing partners in the cytoplasm, it was also an unexpected finding that the nucleus contains more than 30 actin-binding proteins and new classes of actin-related proteins which are not able to form filaments but had evolved nuclear-specific functions. The actin-binding and actin-related proteins in the nucleus have been linked to RNA transcription and processing, nuclear transport, and chromatin remodeling. In this paper, we attempt to provide an overview of the wide range of information that is now available about actin, actin-binding, and actin-related proteins in the nucleus.
Topics: Actins; Animals; Cell Nucleolus; Humans; Microfilament Proteins
PubMed: 26847179
DOI: 10.1007/s00418-015-1400-9 -
Journal of Clinical Laboratory Analysis Feb 2021To detect the expression levels of actin-binding protein anillin (ANLN) in human gastric cancer (GC) tissues and explore the possible involvement of ANLN in GC cell...
BACKGROUND
To detect the expression levels of actin-binding protein anillin (ANLN) in human gastric cancer (GC) tissues and explore the possible involvement of ANLN in GC cell proliferation, migration, and invasion.
METHODS
The bioinformation analysis was performed in TCGA database to explore the expression of ANLN in human GC tissues and the difference of ANLN expression between multiple types of cancers. IHC assays and clinical pathological analysis were performed to confirm ANLN expression and its correlation with clinical features of GC patients. Colony formation, CCK-8, wound closure, and transwell assays were performed to detect its effects on GC cell proliferation, migration, and invasion in vitro. Tumor growth was also measured using a xenograft animal model.
RESULTS
We found the high expression of ANLN in human GC tissues based on the results from TCGA database and IHC staining. We further noticed ANLN depletion resulted in the inhibition of GC cell proliferation, migration, and invasion. Our data further confirmed that ANLN contributed to tumor growth of GC cells in vivo.
CONCLUSIONS
We confirmed the involvement of ANLN in GC progression and thought ANLN could serve as a promising therapeutic target for GC.
Topics: Animals; Cell Line, Tumor; Cell Movement; Cell Proliferation; Female; Humans; Male; Mice, Nude; Microfilament Proteins; Middle Aged; Stomach Neoplasms; Xenograft Model Antitumor Assays; Mice
PubMed: 33089886
DOI: 10.1002/jcla.23635 -
International Journal of Molecular... Feb 2022Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which... (Review)
Review
Actin-associated proteins (AAPs) act on monomeric globular actin (G-actin) and polymerized filamentous actin (F-actin) to regulate their dynamics and architectures which ultimately control cell movement, shape change, division; organelle localization and trafficking. Actin-binding proteins (ABPs) are a subset of AAPs. Since actin was discovered as a myosin-activating protein (hence named actin) in 1942, the protein has also been found to be expressed in non-muscle cells, and numerous AAPs continue to be discovered. This review article lists all of the AAPs discovered so far while also allowing readers to sort the list based on the names, sizes, functions, related human diseases, and the dates of discovery. The list also contains links to the UniProt and Protein Atlas databases for accessing further, related details such as protein structures, associated proteins, subcellular localization, the expression levels in cells and tissues, mutations, and pathology. Because the actin cytoskeleton is involved in many pathological processes such as tumorigenesis, invasion, and developmental diseases, small molecules that target actin and AAPs which hold potential to treat these diseases are also listed.
Topics: Actin Cytoskeleton; Actins; Carcinogenesis; Cell Movement; Humans; Microfilament Proteins; Small Molecule Libraries
PubMed: 35216237
DOI: 10.3390/ijms23042118