https://www.cell.com/trends/cell-biology/pdf/0962-8924(92)90174-L.pdf

The small GTP-binding protein rho regulates the assembly of focal adhesions and actin stress fibers in response to growth factors.

The primary structure of the receptor for platelet-derived growth factor (PDGF), determined by means of cloning a cDNA that encodes the murine pre-PDGF receptor, is closely related to that of the v-kit oncogene product and the receptor for macrophage colony stimulating factor (CSF-1). Common structural features include the presence of long sequences that interrupt the tyrosine-specific protein kinase domains of each molecule. The PDGF and CSF-1 receptors also share a characteristic distribution of extracellular cysteine residues. Ubiquitin is covalently bound to the purified PDGF receptor, the human gene for which is on chromosome 5.

Structure of the receptor for platelet-derived growth factor helps define a family of closely related growth factor receptors

Cells crawl in response to external stimuli by extending and remodeling peripheral elastic lamellae in the direction of locomotion. The remodeling requires vectorial assembly of actin subunits into linear polymers at the lamella's leading edge and the crosslinking of the filaments by bifunctional gelation proteins. The disassembly of the crosslinked filaments into short fragments or monomeric subunits away from the leading edge supplies components for the actin assembly reactions that drive protrusion. Cellular proteins that respond to lipid and ionic signals elicited by sensory cues escort actin through this cycle in which filaments are assembled, crosslinked, and disassembled. One class of myosin molecules may contribute to crawling by guiding sensory receptors to the cell surface, and another class may contribute by imposing contractile forces on actin networks in the lamellae.

On the crawling of animal cells

Growth factors: Mechanism of action and relation to oncogenes

There is evidence that the polymerization of actin takes place at the plasma membrane, and that profilactin (profilin/actin complex), the unpolymerized form of actin found in extracts of many non-muscle cells, serves as the immediate precursor. Both isolated profilin and profilactin interact with detergent when analysed by charge shift electrophoresis, indicating that they have amphipathic properties and may be able to interact directly with the plasma membrane. We demonstrate here that isolated profilin, as well as the profilactin complex, interacts with anionic phospholipids. Phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2) was found to be the most active phospholipid, causing a rapid and efficient dissociation of profilactin with a concomitant polymerization of the actin in appropriate conditions. These and other observations suggest the possibility of a relationship between the induction of actin filament formation and the increased activity in the phosphatidylinositol cycle seen as a result of ligand-receptor interactions in various systems.

Specific interaction between phosphatidylinositol 4,5-bisphosphate and profilactin

Platelet-derived growth factor (PDGF) is a mitogen for several cell types in culture. It is documented in this work that one of the earliest effects of PDGF on serum-starved glial cells is an induction of intensive motile activity. Within the first minute after the addition of PDGF thin membrane lamellae grow out around almost all of the cell circumference. Later, circular arrangements of small ruffles appear on the dorsal surface of the cells. These rings of ruffles vary in size and some encircle almost the whole cell. The organization of the peripheral weave of microfilaments in the PDGF-induced advancing lamellae was closely similar to that of normally growing cells. In the regions of the circular arrangements of ruffles there was an extensive reorganization of the surface actin with unusual arrangements of microfilament bundles and polygonal networks. There was also a general intensification of the translocation of membrane ruffles and spikes from the cell periphery towards the centre of the cell, increased micropinocytotic activity and shuttling of intracellular particles.

The effect of platelet-derived growth factor on morphology and motility of human glial cells

A peripheral weave of microfilaments is visualized in human glia cells. In this weave small numbers of microfilaments converge to structures in the cell edge. Similar assemblies of microfilaments seem to be attached to structures on the surface of microspikes. Together with filaments splaying from the paracrystalline arrangement in microspikes, these units make up the peripheral weave. The filaments of the weave come in close contact with each other and with filaments of internal actin fibres.

Visualization of the peripheral weave of microfilaments in glia cells

The microfilament system and malignancy.

This comparative study of myonuclear domain (MND) size in mammalian species representing a 100,000-fold difference in body mass, ranging from 25 g to 2500 kg, was undertaken to improve our understanding of myonuclear organization in skeletal muscle fibres. Myonuclear domain size was calculated from three-dimensional reconstructions in a total of 235 single muscle fibre segments at a fixed sarcomere length. Irrespective of species, the largest MND size was observed in muscle fibres expressing fast myosin heavy chain (MyHC) isoforms, but in the two smallest mammalian species studied (mouse and rat), MND size was not larger in the fast-twitch fibres expressing the IIA MyHC isofom than in the slow-twitch type I fibres. In the larger mammals, the type I fibres always had the smallest average MND size, but contrary to mouse and rat muscles, type IIA fibres had lower mitochondrial enzyme activities than type I fibres. Myonuclear domain size was highly dependent on body mass in the two muscle fibre types expressed in all species, i.e. types I and IIA. Myonuclear domain size increased in muscle fibres expressing both the beta/slow (type I; r = 0.84, P < 0.001) and the fast IIA MyHC isoform (r = 0.90; P < 0.001). Thus, MND size scales with body size and is highly dependent on muscle fibre type, independent of species. However, myosin isoform expression is not the sole protein determining MND size, and other protein systems, such as mitochondrial proteins, may be equally or more important determinants of MND size.

https://physoc.onlinelibrary.wiley.com/doi/pdf/10.1113/expphysiol.2008.043877

Myonuclear domain size and myosin isoform expression in muscle fibres from mammals representing a 100,000-fold difference in body size

Platelets respond to stimulatory agents in general by the formation of long spikelike surface projections built up of tightly bundled microfilaments. During contact stimulation this is followed by a second phase when thin membrane lamellae grow out between the projections. This behaviour resembles that seen for instance in fibroblasts and glial cells, sending out microspikes and lamellipodia as a step in their advancement over solid substrata. Conditions, designed earlier for the preservation and visualization of the fragile organization of microfilaments and microtubules in the peripheral, highly motile parts (leading lamellae) of such cells (Hoglund et al. (1980) J. Musc. Res. Cell Motility, 1:127-146), were used here to produce high-resolution images of the ultrastructural organization of platelets spreading on a solid substratum. This revealed an unexpected arrangement of actin filaments running parallel to the advancing edge, and small tufts of microfilaments on the outside of this edge-bundle. Cytochalasin D caused a regression of the spikelike projections as well as of both types of structures in the advancing platelet lamella and led to the appearance of a dense filamentous mat in juxtaposition to the plasma membrane. Analysis of the actin pools using the DNAase inhibition assay showed that the dramatic reorganizations of actin seen during the two phases of contact stimulation was reflected in a shift in the G/F-actin ratio only during the early phase.

Anna-Stina Höglund

Papers

The effect of platelet-derived growth factor on morphology and motility of human glial cells

Visualization of the peripheral weave of microfilaments in glia cells

The microfilament system and malignancy.

Myonuclear domain size and myosin isoform expression in muscle fibres from mammals representing a 100,000-fold difference in body size

The organization of microfilaments in spreading platelets: A comparison with fibroblasts and glial cells