BBA - Molecular Cell Research (v.1773, #5)

Actin based processes that could determine the cytoplasmic architecture of plant cells by Hannie S. van der Honing; Anne Mie C. Emons; Tijs Ketelaar (604-614).
Actin polymerisation can generate forces that are necessary for cell movement, such as the propulsion of a class of bacteria, including Listeria, and the protrusion of migrating animal cells. Force generation by the actin cytoskeleton in plant cells has not been studied. One process in plant cells that is likely to depend on actin-based force generation is the organisation of the cytoplasm. We compare the function of actin binding proteins of three well-studied mammalian models that depend on actin-based force generation with the function of their homologues in plants. We predict the possible role of these proteins, and thus the role of actin-based force generation, in the production of cytoplasmic organisation in plant cells.
Keywords: Plant cell; Actin; Actin binding protein; Force generation; Cytoplasm;

Myosin at work: Motor adaptations for a variety of cellular functions by Christopher B. O'Connell; Matthew J. Tyska; Mark S. Mooseker (615-630).
Cells have evolved multiple mechanisms to overcome the effects of entropy and diffusion to create a highly ordered environment. For cells to function properly, some components must be anchored to provide a framework or structure. Others must be rapidly transported over long distances to generate asymmetries in cell morphology and composition. To accomplish long-range transport, cells cannot rely on diffusion alone as many large organelles and macromolecular complexes are essentially immobilized by the dense meshwork of the cytosol. One strategy used by cells to overcome diffusion is to harness the free energy liberated by ATP hydrolysis through molecular motors. Myosins are a family of actin based molecular motors that have evolved a variety of ways to contribute to cellular organization through numerous modifications to the manner they convert that free energy into mechanical work.
Keywords: Unconventional myosin; Molecular motor; Actin; Duty ratio;

Profilin isoforms in Dictyostelium discoideum by Rajesh Arasada; Annika Gloss; Budi Tunggal; Jayabalan M. Joseph; Daniela Rieger; Subhanjan Mondal; Jan Faix; Michael Schleicher; Angelika A. Noegel (631-641).
Eukaryotic cells contain a large number of actin binding proteins of different functions, locations and concentrations. They bind either to monomeric actin (G-actin) or to actin filaments (F-actin) and thus regulate the dynamic rearrangement of the actin cytoskeleton. The Dictyostelium discoideum genome harbors representatives of all G-actin binding proteins including actobindin, twinfilin, and profilin. A phylogenetic analysis of all profilins suggests that two distinguishable groups emerged very early in evolution and comprise either vertebrate and viral profilins or profilins from all other organisms. The newly discovered profilin III isoform in D. discoideum shows all functions that are typical for a profilin. However, the concentration of the third isoform in wild type cells reaches only about 0.5% of total profilin. In a yeast-2-hybrid assay profilin III was found to bind specifically to the proline-rich region of the cytoskeleton-associated vasodilator-stimulated phosphoprotein (VASP). Immunolocalization studies showed similar to VASP the profilin III isoform in filopodia and an enrichment at their tips. Cells lacking the profilin III isoform show defects in cell motility during chemotaxis. The low abundance and the specific interaction with VASP argue against a significant actin sequestering function of the profilin III isoform.
Keywords: Actin monomer binding proteins; Profilin I/II; Phylogeny; Biochemical analysis; Mutant analysis;

Malignant cancer cells utilize their intrinsic migratory ability to invade adjacent tissues and the vasculature, and ultimately to metastasize. Cell migration is the sum of multi-step processes initiated by the formation of membrane protrusions in response to migratory and chemotactic stimuli. The driving force for membrane protrusion is localized polymerization of submembrane actin filaments. Recently, several studies revealed that molecules that link migratory signals to the actin cytoskeleton are upregulated in invasive and metastatic cancer cells. In this review, we summarize recent progress on molecular mechanisms of formation of invasive protrusions used by tumor cells, such as lamellipodia and invadopodia, with regard to the functions of key regulatory proteins of the actin cytoskeleton; WASP family proteins, Arp2/3 complex, LIM-kinase, cofilin, and cortactin.
Keywords: Cell motility; Lamellipodia; Invadopodia; WASP family; Cofilin; Cortactin;

ERM proteins in epithelial cell organization and functions by Bruno Fiévet; Daniel Louvard; Monique Arpin (653-660).
ERM (Ezrin, Radixin, Moesin) proteins are membrane–cytoskeleton linkers that regulate the structure and the function of specific domains of the plasma membrane. ERM proteins are expressed in all metazoan analyzed so far. Genetic analysis of ERM protein functions has recently been performed simultaneously in three different organisms, mouse, Drosophila melanogaster and C. elegans. These studies have revealed a remarkable conservation of the protein functions through evolution. Moreover they have shed light on the crucial role these proteins play in various physiological processes that occur in epithelial cells.
Keywords: Epithelial cell; Morphogenesis; ERM protein; Membrane–cytoskeleton interaction;

A-type lamin networks in light of laminopathic diseases by Sylvia Vlcek; Roland Foisner (661-674).
Lamins are major structural components of the lamina providing mechanical support for the nuclear envelope in vertebrates. A subgroup of lamins, the A-type lamins, are only expressed in differentiated cells and serve important functions both at the nuclear envelope and in the nucleoplasm in higher order chromatin organization and gene regulation. Mutations in A-type lamins cause a variety of diseases from muscular dystrophy and lipodystrophy to systemic diseases such as premature ageing syndromes. The molecular basis of these diseases is still unknown. Here we summarize known interactions of A-type lamins with components of the nuclear envelope and the nucleoplasm and discuss their potential involvement in the etiology and molecular mechanisms of the diseases. Lamin binding partners involve chromatin proteins potentially involved in higher order chromatin organization, transcriptional regulators controlling gene expression during cell cycle progression, differentiation and senescence, and several enzymes involved in a multitude of functions.
Keywords: Cell cycle; Chromosome; Differentiation; Laminopathy; Lamin; Transcription factor;

Role of nuclear lamina-cytoskeleton interactions in the maintenance of cellular strength by F. Houben; F.C.S. Ramaekers; L.H.E.H. Snoeckx; J.L.V. Broers (675-686).
The response of individual cells to cellular stress is vital for cellular functioning. A large network of physically interconnected cellular components, starting from the structural components of the cells' nucleus, via cytoskeleton filaments to adhesion molecules and the extracellular matrix, constitutes an integrated matrix that functions as a scaffold allowing the cell to cope with mechanical stress. Next to a role in mechanical properties, this network also has a mechanotransductional function in the response to mechanical stress. This signaling route does not only regulate a rapid reorganization of structural components such as actin filaments, but also stimulates for example gene activation via NFκB and other transcription factors. The importance of an intact mechano-signaling network is illustrated by the physiological consequences of several genetic defects of cellular network components e.g. actin, dystrophin, desmin and lamins. These give rise to an impaired response of the affected cells to mechanical stress and often result in dystrophy of the affected tissue. Recently, the importance of the cell nucleus in cellular strength has been established. Several new interconnecting proteins, such as the nesprins that link the nuclear lamina to the cytoskeleton, have been identified. Furthermore, the function of nuclear lamins in determining cellular strength and nuclear stability was illustrated in lamin-knock-out cells. Absence of the A-type lamins or mutations in these structural components of the nuclear lamina lead to an impaired cellular response to mechanical stress and disturbances in cytoskeletal organization. In addition, laminopathies show clinical phenotypes comparable to those seen for diseases resulting from genetic defects in cytoskeletal components, further indicating that lamins play a central role in maintaining the mechanical properties of the cell.
Keywords: Tensegrity; Cellular mechanics; Lamins; Laminopathies; Cytoskeleton;