-
Journal of Biochemistry Apr 2021The nucleus is a very complex organelle present in eukaryotic cells. Having the crucial task to safeguard, organize and manage the genetic information, it must tightly... (Review)
Review
The nucleus is a very complex organelle present in eukaryotic cells. Having the crucial task to safeguard, organize and manage the genetic information, it must tightly control its molecular constituents, its shape and its internal architecture at any given time. Despite our vast knowledge of nuclear cell biology, much is yet to be unravelled. For instance, only recently we came to appreciate the existence of a dynamic nuclear cytoskeleton made of actin filaments that regulates processes such as gene expression, DNA repair and nuclear expansion. This suggests further exciting discoveries ahead of us. Modern cell biologists embrace a new methodology relying on precise perturbations of cellular processes that require a reversible, highly spatially confinable, rapid, inexpensive and tunEable external stimulus: light. In this review, we discuss how optogenetics, the state-of-the-art technology that uses genetically encoded light-sensitive proteins to steer biological processes, can be adopted to specifically investigate nuclear cell biology.
Topics: Actin Cytoskeleton; Animals; Cell Biology; Cell Nucleus; Cytoskeleton; Gene Expression Regulation; Humans; Light; Optogenetics; Protein Engineering; Protein Transport
PubMed: 33245128
DOI: 10.1093/jb/mvaa139 -
Annual Review of Cell and Developmental... Oct 2020Many fundamental cellular processes such as division, polarization, endocytosis, and motility require the assembly, maintenance, and disassembly of filamentous actin... (Review)
Review
Many fundamental cellular processes such as division, polarization, endocytosis, and motility require the assembly, maintenance, and disassembly of filamentous actin (F-actin) networks at specific locations and times within the cell. The particular function of each network is governed by F-actin organization, size, and density as well as by its dynamics. The distinct characteristics of different F-actin networks are determined through the coordinated actions of specific sets of actin-binding proteins (ABPs). Furthermore, a cell typically assembles and uses multiple F-actin networks simultaneously within a common cytoplasm, so these networks must self-organize from a common pool of shared globular actin (G-actin) monomers and overlapping sets of ABPs. Recent advances in multicolor imaging and analysis of ABPs and their associated F-actin networks in cells, as well as the development of sophisticated in vitro reconstitutions of networks with ensembles of ABPs, have allowed the field to start uncovering the underlying principles by which cells self-organize diverse F-actin networks to execute basic cellular functions.
Topics: Actin Cytoskeleton; Actins; Animals; Humans; Microfilament Proteins; Models, Biological; Schizosaccharomyces
PubMed: 33021819
DOI: 10.1146/annurev-cellbio-032320-094706 -
Genes Jan 2023The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical... (Review)
Review
The mechanical properties of cells are important in tissue homeostasis and enable cell growth, division, migration and the epithelial-mesenchymal transition. Mechanical properties are determined to a large extent by the cytoskeleton. The cytoskeleton is a complex and dynamic network composed of microfilaments, intermediate filaments and microtubules. These cellular structures confer both cell shape and mechanical properties. The architecture of the networks formed by the cytoskeleton is regulated by several pathways, a key one being the Rho-kinase/ROCK signaling pathway. This review describes the role of ROCK (Rho-associated coiled-coil forming kinase) and how it mediates effects on the key components of the cytoskeleton that are critical for cell behaviour.
Topics: rho-Associated Kinases; Cytoskeleton; Microtubules; Signal Transduction; Actin Cytoskeleton
PubMed: 36833199
DOI: 10.3390/genes14020272 -
Seminars in Cell & Developmental Biology Jun 2020Actin filaments (F-actin) are a key component of eukaryotic cells. Whether serving as a scaffold for myosin or using their polymerization to push onto cellular... (Review)
Review
Actin filaments (F-actin) are a key component of eukaryotic cells. Whether serving as a scaffold for myosin or using their polymerization to push onto cellular components, their function is always related to force generation. To control and fine-tune force production, cells have a large array of actin-binding proteins (ABPs) dedicated to control every aspect of actin polymerization, filament localization, and their overall mechanical properties. Although great advances have been made in our biochemical understanding of the remodeling of the actin cytoskeleton, the structural basis of this process is still being deciphered. In this review, we summarize our current understanding of this process. We outline how ABPs control the nucleation and disassembly, and how these processes are affected by the nucleotide state of the filaments. In addition, we highlight recent advances in the understanding of actomyosin force generation, and describe recent advances brought forward by the developments of electron cryomicroscopy.
Topics: Actin Cytoskeleton; Animals; Humans; Models, Molecular; Molecular Structure
PubMed: 31836290
DOI: 10.1016/j.semcdb.2019.11.018 -
Anatomical Record (Hoboken, N.J. : 2007) Dec 2018Cytokinesis and single-cell wound repair both involve contractile assemblies of filamentous actin (F-actin) and myosin II organized into characteristic ring-like arrays.... (Review)
Review
Cytokinesis and single-cell wound repair both involve contractile assemblies of filamentous actin (F-actin) and myosin II organized into characteristic ring-like arrays. The assembly of these actomyosin contractile rings (CRs) is specified spatially and temporally by small Rho GTPases, which trigger local actin polymerization and myosin II contractility via a variety of downstream effectors. We now have a much clearer view of the Rho GTPase signaling cascade that leads to the formation of CRs, but some factors involved in CR positioning, assembly, and function remain poorly understood. Recent studies show that this regulation is multifactorial and goes beyond the long-established Ca -dependent processes. There is substantial evidence that the Ca -independent changes in cell shape, tension, and plasma membrane composition that characterize cytokinesis and single-cell wound repair also regulate CR formation. Elucidating the regulation and mechanistic properties of CRs is important to our understanding of basic cell biology and holds potential for therapeutic applications in human disease. In this review, we present a primer on the factors influencing and regulating CR positioning, assembly, and contraction as they occur in a variety of cytokinetic and single-cell wound repair models. Anat Rec, 301:2051-2066, 2018. © 2018 Wiley Periodicals, Inc.
Topics: Actin Cytoskeleton; Actomyosin; Animals; Cell Membrane; Contractile Proteins; Cytokinesis; Humans; Tissue Scaffolds; Wound Healing
PubMed: 30312008
DOI: 10.1002/ar.23962 -
Frontiers in Immunology 2022Actin is an important cytoskeletal protein involved in signal transduction, cell structure and motility. Actin regulators include actin-monomer-binding proteins,... (Review)
Review
Actin is an important cytoskeletal protein involved in signal transduction, cell structure and motility. Actin regulators include actin-monomer-binding proteins, Wiskott-Aldrich syndrome (WAS) family of proteins, nucleation proteins, actin filament polymerases and severing proteins. This group of proteins regulate the dynamic changes in actin assembly/disassembly, thus playing an important role in cell motility, intracellular transport, cell division and other basic cellular activities. Lymphocytes are important components of the human immune system, consisting of T-lymphocytes (T cells), B-lymphocytes (B cells) and natural killer cells (NK cells). Lymphocytes are indispensable for both innate and adaptive immunity and cannot function normally without various actin regulators. In this review, we first briefly introduce the structure and fundamental functions of a variety of well-known and newly discovered actin regulators, then we highlight the role of actin regulators in T cell, B cell and NK cell, and finally provide a landscape of various diseases associated with them. This review provides new directions in exploring actin regulators and promotes more precise and effective treatments for related diseases.
Topics: Actin Cytoskeleton; Actins; Humans; Microfilament Proteins; T-Lymphocytes; Wiskott-Aldrich Syndrome; Wiskott-Aldrich Syndrome Protein
PubMed: 35371070
DOI: 10.3389/fimmu.2022.799309 -
Molecular Biology of the Cell Nov 2023Most eukaryotic cells utilize clathrin-mediated endocytosis as well as multiple clathrin-independent pathways to internalize proteins and membranes. Although...
Most eukaryotic cells utilize clathrin-mediated endocytosis as well as multiple clathrin-independent pathways to internalize proteins and membranes. Although clathrin-mediated endocytosis has been studied extensively and many machinery proteins have been identified, clathrin-independent pathways remain poorly characterized by comparison. We previously identified the first known yeast clathrin-independent endocytic pathway, which relies on the actin-modulating GTPase Rho1, the formin Bni1 and unbranched actin filaments, but does not require the clathrin coat or core clathrin machinery proteins. In this study, we sought to better understand clathrin-independent endocytosis in yeast by exploring the role of myosins as actin-based motors, because actin is required for endocytosis in yeast. We find that Myo2, which transports secretory vesicles, organelles and microtubules along actin cables to sites of polarized growth, participates in clathrin-independent endocytosis. Unexpectedly, the ability of Myo2 to transport microtubule plus ends to the cell cortex appears to be required for its role in clathrin-independent endocytosis. In addition, dynein, dynactin, and proteins involved in cortical microtubule capture are also required. Thus, our results suggest that interplay between actin and microtubules contributes to clathrin-independent internalization in yeast.
Topics: Saccharomyces cerevisiae; Actins; Clathrin; Microtubules; Endocytosis; Actin Cytoskeleton; Microfilament Proteins; Saccharomyces cerevisiae Proteins
PubMed: 37647159
DOI: 10.1091/mbc.E23-05-0164 -
Archives of Biochemistry and Biophysics Oct 2017MICAL (from the Molecule Interacting with CasL) indicates a family of multidomain proteins conserved from insects to humans, which are increasingly attracting attention... (Review)
Review
MICAL (from the Molecule Interacting with CasL) indicates a family of multidomain proteins conserved from insects to humans, which are increasingly attracting attention for their participation in the control of actin cytoskeleton dynamics, and, therefore, in the several related key processes in health and disease. MICAL is unique among actin binding proteins because it catalyzes a NADPH-dependent F-actin depolymerizing reaction. This unprecedented reaction is associated with its N-terminal FAD-containing domain that is structurally related to p-hydroxybenzoate hydroxylase, the prototype of aromatic monooxygenases, but catalyzes a strong NADPH oxidase activity in the free state. This review will focus on the known structural and functional properties of MICAL forms in order to provide an overview of the arguments supporting the current hypotheses on the possible mechanism of action of MICAL in the free and F-actin bound state, on the modulating effect of the CH, LIM, and C-terminal domains that follow the catalytic flavoprotein domain on the MICAL activities, as well as that of small molecules and proteins interacting with MICAL.
Topics: Actin Cytoskeleton; Actins; Adaptor Proteins, Signal Transducing; Animals; Cytoskeletal Proteins; Flavoproteins; Humans; LIM Domain Proteins; Microfilament Proteins; Mixed Function Oxygenases; NADP; Protein Domains; Structure-Activity Relationship
PubMed: 28602956
DOI: 10.1016/j.abb.2017.06.004 -
Developmental Cell Dec 2014Cytokinesis mediates the physical separation of dividing cells after chromosome segregation. In animal cell cytokinesis, a contractile ring, mainly composed of actin and... (Review)
Review
Cytokinesis mediates the physical separation of dividing cells after chromosome segregation. In animal cell cytokinesis, a contractile ring, mainly composed of actin and myosin filaments, ingresses a cleavage furrow midway between the two spindle poles. A distinct machinery, involving the endosomal sorting complex required for transport III (ESCRT-III), subsequently splits the plasma membrane of nascent daughter cells in a process termed abscission. Here, we provide a brief overview of early cytokinesis events in animal cells and then cover in depth recently emerging models for the assembly and function of the abscission machinery and its temporal coordination with chromosome segregation.
Topics: Actin Cytoskeleton; Animals; Cell Membrane; Cell Proliferation; Chromosome Segregation; Cytokinesis; Endosomal Sorting Complexes Required for Transport; Humans
PubMed: 25490264
DOI: 10.1016/j.devcel.2014.11.006 -
Scientific Reports Feb 2022Cortical actin plays a key role in cell movement and division, but has also been implicated in the organisation of cell surface receptors such as G protein-coupled...
Cortical actin plays a key role in cell movement and division, but has also been implicated in the organisation of cell surface receptors such as G protein-coupled receptors. The actin mesh proximal to the inner membrane forms small fenced regions, or 'corrals', in which receptors can be constrained. Quantification of the actin mesh at the nanoscale has largely been attempted in single molecule datasets and electron micrographs. This work describes the development and validation of workflows for analysis of super resolved fixed cortical actin images obtained by Super Resolved Radial Fluctuations (SRRF), Structured Illumination Microscopy (3D-SIM) and Expansion Microscopy (ExM). SRRF analysis was used to show a significant increase in corral area when treating cells with the actin disrupting agent cytochalasin D (increase of 0.31 µm ± 0.04 SEM), and ExM analysis allowed for the quantitation of actin filament densities. Thus, this work allows complex actin networks to be quantified from super-resolved images and is amenable to both fixed and live cell imaging.
Topics: A549 Cells; Actin Cytoskeleton; Actins; Cell Membrane; Cytochalasin D; Humans; Image Processing, Computer-Assisted; Microscopy, Fluorescence
PubMed: 35177729
DOI: 10.1038/s41598-022-06702-w