-
Current Biology : CB May 2021Arit Ghosh and Velia Fowler introduce the structural features and functions of tropomodulins - actin-binding proteins that cap the slow-growing (pointed) ends of actin...
Arit Ghosh and Velia Fowler introduce the structural features and functions of tropomodulins - actin-binding proteins that cap the slow-growing (pointed) ends of actin filaments.
Topics: Actin Cytoskeleton; Actins; Microfilament Proteins; Tropomodulin
PubMed: 34033779
DOI: 10.1016/j.cub.2021.01.055 -
IUBMB Life May 2012Parasites from the phylum Apicomplexa are responsible for several major diseases of man, including malaria and toxoplasmosis. These highly motile protozoa use a... (Review)
Review
Parasites from the phylum Apicomplexa are responsible for several major diseases of man, including malaria and toxoplasmosis. These highly motile protozoa use a conserved actomyosin-based mode of movement to power tissue traversal and host cell invasion. The mode termed as 'gliding motility' relies on the dynamic turnover of actin, whose polymerisation state is controlled by a markedly limited number of identifiable regulators when compared with other eukaryotic cells. Recent studies of apicomplexan actin regulator structure-in particular those of the core triad of monomer-binding proteins, actin-depolymerising factor/cofilin, cyclase-associated protein/Srv2, and profilin-have provided new insights into possible mechanisms of actin regulation in parasite cells, highlighting divergent structural features and functions to regulators from other cellular systems. Furthermore, the unusual nature of apicomplexan actin itself is increasingly coming into the spotlight. Here, we review recent advances in understanding of the structure and function of actin and its regulators in apicomplexan parasites. In particular we explore the paradox between there being an abundance of unpolymerised actin, its having a seemingly increased potential to form filaments relative to vertebrate actin, and the apparent lack of visible, stable filaments in parasite cells.
Topics: Actin Cytoskeleton; Animals; Apicomplexa; Humans; Microfilament Proteins; Protein Binding; Protein Structure, Quaternary; Protozoan Proteins
PubMed: 22454107
DOI: 10.1002/iub.1014 -
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 -
Molecular and Biochemical Parasitology May 2020Trypanosomatids are a monophyletic group of parasitic flagellated protists belonging to the order Kinetoplastida. Their cytoskeleton is primarily made up of microtubules... (Review)
Review
Trypanosomatids are a monophyletic group of parasitic flagellated protists belonging to the order Kinetoplastida. Their cytoskeleton is primarily made up of microtubules in which no actin microfilaments have been detected. Although all these parasites contain actin, it is widely thought that their actin cytoskeleton is reduced when compared to most eukaryotic organisms. However, there is increasing evidence that it is more complex than previously thought. As in other eukaryotic organisms, trypanosomatids encode for a conventional actin that is expected to form microfilament-like structures, and for members of three conserved actin-related proteins probably involved in microfilament nucleation (ARP2, ARP3) and in gene expression regulation (ARP6). In addition to these canonical proteins, also encode for an expanded set of actins and actin-like proteins that seem to be restricted to kinetoplastids. Analysis of their amino acid sequences demonstrated that, although very diverse in primary sequence when compared to actins of model organisms, modelling of their tertiary structure predicted the presence of the actin fold in all of them. Experimental characterization has been done for only a few of the trypanosomatid actins and actin-binding proteins. The most studied is the conventional actin of Leishmania donovani (LdAct), which unusually requires both ATP and Mg for polymerization, unlike other conventional actins that do not require ATP. Additionally, polymerized LdAct tends to assemble in bundles rather than in single filaments. Regulation of actin polymerization depends on their interaction with actin-binding proteins. In trypanosomatids, there is a reduced but sufficient core of actin-binding proteins to promote microfilament nucleation, turnover and stabilization. There are also genes encoding for members of two families of myosin motor proteins, including one lineage-specific. Homologues to all identified actin-family proteins and actin-binding proteins of trypanosomatids are also present in Paratrypanosoma confusum (an early branching trypanosomatid) and in Bodo saltans (a closely related free-living organism belonging to the trypanosomatid sister order of Bodonida) suggesting they were all present in their common ancestor. Secondary losses of these genes may have occurred during speciation within the trypanosomatids, with salivarian trypanosomes having lost many of them and stercorarian trypanosomes retaining most.
Topics: Actin Cytoskeleton; Actins; Animals; Binding Sites; Gene Expression; Humans; Microfilament Proteins; Models, Molecular; Myosins; Phylogeny; Protein Binding; Protein Conformation, alpha-Helical; Protein Conformation, beta-Strand; Protein Interaction Domains and Motifs; Protozoan Proteins; Trypanosomatina
PubMed: 32353561
DOI: 10.1016/j.molbiopara.2020.111278 -
Trends in Biochemical Sciences Jun 2005Formin proteins are potent regulators of actin dynamics. Most eukaryotes have multiple formin isoforms, suggesting diverse cellular roles. Formins are modular proteins,... (Review)
Review
Formin proteins are potent regulators of actin dynamics. Most eukaryotes have multiple formin isoforms, suggesting diverse cellular roles. Formins are modular proteins, containing a series of domains and functional motifs. The Formin homology 2 (FH2) domain binds actin filament barbed ends and moves processively as these barbed ends elongate or depolymerize. The FH1 domain influences FH2 domain function through binding to the actin monomer-binding protein, profilin. Outside of FH1 and FH2, amino acid similarity between formins decreases, suggesting diverse mechanisms for regulation and cellular localization. Some formins are regulated by auto-inhibition through interaction between the diaphanous inhibitory domain (DID) and diaphanous auto-regulatory domain (DAD), and activated by Rho GTPase binding to GTPase-binding domains (GBD). Other formins lack DAD, DID and GBD, and their regulatory mechanisms await elucidation.
Topics: Actins; Animals; Carrier Proteins; Contractile Proteins; Fetal Proteins; Formins; Humans; Microfilament Proteins; Models, Molecular; Nuclear Proteins; Profilins; Protein Structure, Tertiary; Sequence Homology, Amino Acid; rho GTP-Binding Proteins
PubMed: 15950879
DOI: 10.1016/j.tibs.2005.04.014 -
Current Opinion in Structural Biology Apr 1998The study of proteins that bind filamentous actin (F-actin) is entering an exciting stage as more and more structures are determined. After more than 50 years in which... (Review)
Review
The study of proteins that bind filamentous actin (F-actin) is entering an exciting stage as more and more structures are determined. After more than 50 years in which the focus was on muscle proteins, emphasis has recently shifted towards understanding the complex interplay among actin-binding molecules in non-muscle cells. To date, the binding sites for eight classes of filament-binding molecules have been determined by combining low- to intermediate-resolution maps obtained by electron microscopy with atomic structures determined by X-ray crystallography and NMR. Recent results have dramatically accentuated the importance of filament geometry and actin conformation in defining these interactions.
Topics: Actin Depolymerizing Factors; Actins; Animals; Binding Sites; Carrier Proteins; Cross-Linking Reagents; Crystallography, X-Ray; Gelsolin; Macromolecular Substances; Microfilament Proteins; Microscopy, Electron; Models, Molecular; Muscle Contraction; Protein Binding
PubMed: 9631289
DOI: 10.1016/s0959-440x(98)80034-1 -
Cytoskeleton (Hoboken, N.J.) Jan 2023
Topics: Actins; Binding Sites; Microfilament Proteins
PubMed: 36579710
DOI: 10.1002/cm.21739 -
The International Journal of... Jan 2004Tensin is a cytoplasmic phosphoprotein that localized to integrin-mediated focal adhesions. It binds to actin filaments and contains a phosphotyrosine-binding (PTB)... (Review)
Review
Tensin is a cytoplasmic phosphoprotein that localized to integrin-mediated focal adhesions. It binds to actin filaments and contains a phosphotyrosine-binding (PTB) domain, which interacts with the cytoplasmic tails of beta integrin. These interactions allow tensin to link actin filaments to integrin receptors. In addition, tensin has an Src Homology 2 (SH2) domain capable of interacting with tyrosine-phosphorylated proteins. Furthermore, several factors induce tyrosine phosphorylation of tensin. Thus, tensin functions as a platform for dis/assembly of signaling complexes at focal adhesions by recruiting tyrosine-phosphorylated signaling molecules through the SH2 domain, and also by providing interaction sites for other SH2-containing proteins. Analysis of knockout mice has demonstrated critical roles of tensin in renal function, muscle regeneration, and cell migration. Therefore, tensin and its downstream signaling molecules may be targets for therapeutic interventions in renal disease, wound healing and cancer.
Topics: Actins; Animals; Binding Sites; Focal Adhesions; Gene Expression; Humans; Microfilament Proteins; Phosphorylation; Phosphotyrosine; Protein Structure, Tertiary; Substrate Specificity; Tensins; Tissue Distribution; Tyrosine; src Homology Domains
PubMed: 14592531
DOI: 10.1016/s1357-2725(03)00171-7 -
Progress in Biophysics and Molecular... Nov 2022Actopaxin is a newly discovered focal adhesions (FAs) protein, actin-binding protein and pseudopodia-enriched molecule. It can not only bind to a variety of FAs proteins... (Review)
Review
Actopaxin is a newly discovered focal adhesions (FAs) protein, actin-binding protein and pseudopodia-enriched molecule. It can not only bind to a variety of FAs proteins (such as Paxillin, ILK and PINCH) and non-FAs proteins (such as TESK1, CdGAP, β2-adaptin, G3BP2, ADAR1 and CD29), but also participates in multiple signaling pathways. Thus, it plays a crucial role in regulating important processes of tumor metastasis, including matrix degradation, migration, and invasion, etc. This review covers the latest progress in the structure and function of Actopaxin, its interaction with other proteins as well as its involvement in regulating tumor development and metastasis. Additionally, the current limitations for Actopaxin related studies and the possible research directions on it in the future are also discussed. It is hoped that this review can assist relevant researchers to obtain a deep understanding of the role that Actopaxin plays in tumor progression, and also enlighten further research and development of therapeutic approaches for the treatment of tumor metastasis.
Topics: Humans; Actinin; Cell Movement; Focal Adhesions; Microfilament Proteins; Neoplasms
PubMed: 36150525
DOI: 10.1016/j.pbiomolbio.2022.09.006 -
Current Opinion in Cell Biology Feb 1993Recent research on F-actin capping proteins has concentrated on three main areas. The discovery that controlled actin polymerization is the driving force for... (Review)
Review
Recent research on F-actin capping proteins has concentrated on three main areas. The discovery that controlled actin polymerization is the driving force for intracellular movement suggests an important role for capping proteins in regulating filament number and length. A capping protein from Dictyostelium (related to heat-shock protein HSP70) has been characterized that is activated by external stimuli. This provides a pivotal connection between extracellular signalling, cytoskeletal reorganization and locomotory behaviour. The roles of individual actin-binding sites in the gelsolin family of severing/capping proteins and binding sites for phosphatidylinositol 4,5-bisphosphate have been identified.
Topics: Actins; Amino Acid Sequence; Animals; Binding Sites; Cell Movement; Fungal Proteins; Kinetics; Microfilament Proteins; Molecular Sequence Data; Molecular Structure; Phosphatidylinositol 4,5-Diphosphate; Phosphatidylinositols; Phosphorylation; Polymers; Protein Binding; Signal Transduction
PubMed: 8383512
DOI: 10.1016/s0955-0674(05)80009-2