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Biochimica Et Biophysica Acta Feb 2010The regulation of the actin cytoskeleton is a key process for the stability and motility of eukaryotic cells. Besides the Arp2/3 complex and its nucleation promoting... (Review)
Review
The regulation of the actin cytoskeleton is a key process for the stability and motility of eukaryotic cells. Besides the Arp2/3 complex and its nucleation promoting factors, WH2 domain-containing proteins and a diverse family of formin proteins have recently been recognized as actin nucleators and potent polymerization factors of actin filaments. Formins are defined by the presence of a catalytic formin homology 2 (FH2) domain, yet, the modular domain architecture appears significantly different for the eight formin families identified in humans. A diverse picture of protein localization, interaction partners and cell specific regulation emerged, suggesting various functions of formins in the building and maintenance of actin filaments. This review focuses on the domain architecture of human formins, the regulation mechanisms of their activation and the diversity in formin cellular functions.
Topics: Actin Cytoskeleton; Animals; Cytoskeleton; Fetal Proteins; Formins; Humans; Microfilament Proteins; Models, Molecular; Nuclear Proteins; Phylogeny; Protein Structure, Tertiary
PubMed: 20102729
DOI: 10.1016/j.bbamcr.2010.01.014 -
Small GTPases 2014Eukaryotic cells have evolved a variety of actin-binding proteins to regulate the architecture and the dynamics of the actin cytoskeleton in time and space. The... (Review)
Review
Eukaryotic cells have evolved a variety of actin-binding proteins to regulate the architecture and the dynamics of the actin cytoskeleton in time and space. The Diaphanous-related formins (DRF) represent a diverse group of Rho-GTPase-regulated actin regulators that control a range of actin structures composed of tightly-bundled, unbranched actin filaments as found in stress fibers and in filopodia. Under resting conditions, DRFs are auto-inhibited by an intra-molecular interaction between the C-terminal and the N-terminal domains. The auto-inhibition is thought to be released by binding of an activated RhoGTPase to the N-terminal GTPase-binding domain (GBD). However, there is growing evidence for more sophisticated variations from this simplified linear activation model. In this review we focus on the formin homology domain-containing proteins (FHOD), an unconventional group of DRFs. Recent findings on the molecular control and cellular functions of FHOD proteins in vivo are discussed in the light of the phylogeny of FHOD proteins.
Topics: Actin Cytoskeleton; Animals; Humans; Microfilament Proteins; Protein Structure, Tertiary; rho GTP-Binding Proteins
PubMed: 25483300
DOI: 10.4161/21541248.2014.973765 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018The actin cytoskeleton has long been recognized as a crucial sub-cellular filament system that is responsible for governing fundamental events ranging from cell division...
The actin cytoskeleton has long been recognized as a crucial sub-cellular filament system that is responsible for governing fundamental events ranging from cell division and muscle contraction to whole cell motility and the maintenance of tissue integrity. Consequently, it is not surprising that this network is the focus of over 100,000 different manuscripts. Alterations in the actin cytoskeleton lead to an assortment of diseases and serve as a target for a variety of pathogens. Here we have brought together a collection of primary research articles and reviews that underscore the broad influence this filament system has on organisms. Anat Rec, 301:1986-1990, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actin Cytoskeleton; Actins; Animals; Cell Movement; Humans; Microfilament Proteins
PubMed: 30312025
DOI: 10.1002/ar.23960 -
Genome Biology 2002The ADF/cofilins are a family of actin-binding proteins expressed in all eukaryotic cells so far examined. Members of this family remodel the actin cytoskeleton, for... (Review)
Review
The ADF/cofilins are a family of actin-binding proteins expressed in all eukaryotic cells so far examined. Members of this family remodel the actin cytoskeleton, for example during cytokinesis, when the actin-rich contractile ring shrinks as it contracts through the interaction of ADF/cofilins with both monomeric and filamentous actin. The depolymerizing activity is twofold: ADF/cofilins sever actin filaments and also increase the rate at which monomers leave the filament's pointed end. The three-dimensional structure of ADF/cofilins is similar to a fold in members of the gelsolin family of actin-binding proteins in which this fold is typically repeated three or six times; although both families bind polyphosphoinositide lipids and actin in a pH-dependent manner, they share no obvious sequence similarity. Plants and animals have multiple ADF/cofilin genes, belonging in vertebrates to two types, ADF and cofilins. Other eukaryotes (such as yeast, Acanthamoeba and slime moulds) have a single ADF/cofilin gene. Phylogenetic analysis of the ADF/cofilins reveals that, with few exceptions, their relationships reflect conventional views of the relationships between the major groups of organisms.
Topics: Actin Depolymerizing Factors; Actins; Animals; Cofilin 2; Destrin; Evolution, Molecular; Exons; Gene Expression Regulation; Humans; Introns; Microfilament Proteins; Multigene Family
PubMed: 12049672
DOI: 10.1186/gb-2002-3-5-reviews3007 -
Current Biology : CB Jul 2011Eukaryotic cells generate a diversity of actin filament networks in a common cytoplasm to optimally perform functions such as cell motility, cell adhesion, endocytosis... (Review)
Review
Eukaryotic cells generate a diversity of actin filament networks in a common cytoplasm to optimally perform functions such as cell motility, cell adhesion, endocytosis and cytokinesis. Each of these networks maintains precise mechanical and dynamic properties by autonomously controlling the composition of its interacting proteins and spatial organization of its actin filaments. In this review, we discuss the chemical and physical mechanisms that target distinct sets of actin-binding proteins to distinct actin filament populations after nucleation, resulting in the assembly of actin filament networks that are optimized for specific functions.
Topics: Actin Cytoskeleton; Animals; Cytoplasm; Microfilament Proteins; Models, Biological; Yeasts
PubMed: 21783039
DOI: 10.1016/j.cub.2011.06.019 -
Current Opinion in Cell Biology Feb 2009Cells require actin nucleators to catalyze the de novo assembly of filaments and actin elongation factors to control the rate and extent of polymerization. Nucleation... (Review)
Review
Cells require actin nucleators to catalyze the de novo assembly of filaments and actin elongation factors to control the rate and extent of polymerization. Nucleation and elongation factors identified to date include Arp2/3 complex, formins, Ena/VASP, and newcomers Spire, Cobl, and Lmod. Here, we discuss recent advances in understanding their activities and mechanisms and new evidence for their cooperation and interaction in vivo. Earlier models had suggested that different nucleators function independently to assemble distinct actin arrays. However, more recent observations indicate that the construction of most cellular actin networks depends on the activities of multiple actin assembly-promoting factors working in concert.
Topics: Actin Depolymerizing Factors; Actin-Related Protein 2-3 Complex; Actins; Animals; Cell Physiological Phenomena; Cytoskeleton; Microfilament Proteins
PubMed: 19168341
DOI: 10.1016/j.ceb.2008.12.001 -
Cellular and Molecular Life Sciences :... Jul 2009During gene expression, multiple regulatory steps make sure that alterations of chromatin structure are synchronized with RNA synthesis, co-transcriptional assembly of... (Review)
Review
During gene expression, multiple regulatory steps make sure that alterations of chromatin structure are synchronized with RNA synthesis, co-transcriptional assembly of ribonucleoprotein complexes, transport to the cytoplasm and localized translation. These events are controlled by large multiprotein complexes commonly referred to as molecular machines, which are specialized and at the same time display a highly dynamic protein composition. The crosstalk between these molecular machines is essential for efficient RNA biogenesis. Actin has been recently proposed to be an important factor throughout the entire RNA biogenesis pathway as a component of chromatin remodeling complexes, associated with all eukaryotic RNA polymerases as well as precursor and mature ribonucleoprotein complexes. The aim of this review is to present evidence on the involvement of actin and actin-associated proteins in RNA biogenesis and propose integrative models supporting the view that actin facilitates coordination of the different steps in gene expression.
Topics: Actins; Animals; Gene Expression Regulation; Humans; Microfilament Proteins; Myosins; Polyribosomes; RNA; Ribonucleoproteins
PubMed: 19300907
DOI: 10.1007/s00018-009-0012-8 -
Critical Reviews in Biochemistry and... 2009The spontaneous and unregulated polymerization of actin filaments is inhibited in cells by actin monomer-binding proteins such as profilin and Tbeta4. Eukaryotic cells... (Review)
Review
The spontaneous and unregulated polymerization of actin filaments is inhibited in cells by actin monomer-binding proteins such as profilin and Tbeta4. Eukaryotic cells and certain pathogens use filament nucleators to stabilize actin polymerization nuclei, whose formation is rate-limiting. Known filament nucleators include the Arp2/3 complex and its large family of nucleation promoting factors (NPFs), formins, Spire, Cobl, VopL/VopF, TARP and Lmod. These molecules control the time and location for polymerization, and additionally influence the structures of the actin networks that they generate. Filament nucleators are generally unrelated, but with the exception of formins they all use the WASP-Homology 2 domain (WH2 or W), a small and versatile actin-binding motif, for interaction with actin. A common architecture, found in Spire, Cobl and VopL/VopF, consists of tandem W domains that bind three to four actin subunits to form a nucleus. Structural considerations suggest that NPFs-Arp2/3 complex can also be viewed as a specialized form of tandem W-based nucleator. Formins are unique in that they use the formin-homology 2 (FH2) domain for interaction with actin and promote not only nucleation, but also processive barbed end elongation. In contrast, the elongation function among W-based nucleators has been "outsourced" to a dedicated family of proteins, Eva/VASP, which are related to WASP-family NPFs.
Topics: Actin Cytoskeleton; Animals; Humans; Microfilament Proteins; Models, Biological; Protein Conformation; Protein Multimerization
PubMed: 19874150
DOI: 10.3109/10409230903277340 -
Philosophical Transactions of the Royal... Feb 2002Fibrillins form the structural framework of a unique and essential class of extracellular microfibrils that endow dynamic connective tissues with long-range elasticity.... (Review)
Review
Fibrillins form the structural framework of a unique and essential class of extracellular microfibrils that endow dynamic connective tissues with long-range elasticity. Their biological importance is emphasized by the linkage of fibrillin mutations to Marfan syndrome and related connective tissue disorders, which are associated with severe cardiovascular, ocular and skeletal defects. These microfibrils have a complex ultrastructure and it has proved a major challenge both to define their structural organization and to relate it to their biological function. However, new approaches have at last begun to reveal important insights into their molecular assembly, structural organization and biomechanical properties. This paper describes the current understanding of the molecular assembly of fibrillin molecules, the alignment of fibrillin molecules within microfibrils and the unique elastomeric properties of microfibrils.
Topics: Animals; Biomechanical Phenomena; Elasticity; Fibrillins; Humans; Marfan Syndrome; Microfibrils; Microfilament Proteins; Models, Molecular; Protein Structure, Quaternary
PubMed: 11911778
DOI: 10.1098/rstb.2001.1029 -
Nucleus (Austin, Tex.) 2011The actin family consists of conventional actin and actin-related proteins (ARPs), and the members show moderate similarity and share the same basal structure. Following... (Review)
Review
The actin family consists of conventional actin and actin-related proteins (ARPs), and the members show moderate similarity and share the same basal structure. Following the finding of various ARPs in the cytoplasm in the 1990s, multiple subfamilies that are localized predominantly in the nucleus were identified. Consistent with these cytological observations, subsequent biochemical analyses revealed the involvement of the nuclear ARPs in ATP-dependent chromatin-remodeling and histone acetyltransferase complexes. In addition to their contribution to chromatin remodeling, recent studies have shown that nuclear ARPs have roles in the organization of the nucleus that are independent of the activity of the above-mentioned complexes. Therefore, nuclear ARPs are recognized as novel key regulators of genome function, and affect not only the remodeling of chromatin but also the spatial arrangement and dynamics of chromatin within the nucleus.
Topics: Actins; Cell Nucleus; Chromatin; Chromatin Assembly and Disassembly; Histones; Humans; Microfilament Proteins
PubMed: 21647298
DOI: 10.4161/nucl.2.1.14510