Life implies movement. Most forms of movement in the living world are powered by tiny protein machines known as molecular motors. Among the best known are motors that use sophisticated intramolecular amplification mechanisms to take nanometre steps along protein tracks in the cytoplasm. These motors transport a wide variety of cargo, power cell locomotion, drive cell division and, when combined in large ensembles, allow organisms to move. Motor defects can lead to severe diseases or may even be lethal. Basic principles of motor design and mechanism have now been derived, and an understanding of their complex cellular roles is emerging.

Abstract. The cytoplasm of vertebrate cells contains three distinct filamentous biopolymers, the microtubules, microfilaments, and intermediate filaments. The basic structural elements of these three filaments are linear polymers of the proteins tubulin, actin, and vimentin or another related intermediate filament protein, respectively. The viscoelastic properties of cytoplasmic filaments are likely to be relevant to their biologic function, because their extreme length and rodlike structure dominate the rheologic behavior of cytoplasm, and changes in their structure may cause gel-sol transitions observed when cells are activated or begin to move. This paper describes parallel measurements of the viscoelasticity of tubulin, actin, and vimentin polymers. The rheologic differences among the three types of cytoplasmic polymers suggest possible specialized roles for the different classes of iliaments in vivo. Actin forms networks of highest rigidity that fluidize at high strains, consistent with a role in cell motility in which stable protrusions can deform rapidly in response to controlled filament rupture. Vimentin networks, which have not previously been studied by rheologic methods, exhibit some unusual viscoelastic properties not shared by actin or tubulin. They are less rigid (have lower shear moduli) at low strain but harden at high strains and resist breakage, suggesting they maintain cell integrity. The differences between F-actin and vimentin are optimal for the formation of a composite material with a range of properties that cannot be achieved by either polymer alone. Microtubules are unlikely to contribute significantly to interphase cell rheology alone, but may help stabilize the other networks.T HRE~ classes of filaments, microfilaments, microtubules, and intermediate filaments, collectively termed the cytoskeleton permeate the cytoplasmic space, constitute a large fraction of total cell protein, and are believed to endow the cell with the elasticity needed to resist mechanical forces encountered in vivo (Bershadsky and Vasiliev,

In recent years the kinesin superfamily has become so large that several different naming schemes have emerged, leading to confusion and miscommunication. Here, we set forth a standardized kinesin nomenclature based on 14 family designations. The scheme unifies all previous phylogenies and nomenclature proposals, while allowing individual sequence names to remain the same, and for expansion to occur as new sequences are discovered.

Extraction of BSC-1 cells (African green monkey kidney) with the detergent Triton X-100 in combination with stereo high-voltage electron microscopy of whole mount preparations has been used as an approach to determine the mode of action of cytochalasin D on cells. The cytoskeleton of extracted BSC-1 cells consists of substrate-associated filament bundles (stress fibers) and a highly cross-linked network of four major filament types extending throughout the cell body : 10-nm filaments, actin microfilaments, microtubules, and 2-to 3-nm filaments . Actin filaments and 2-to 3-nm filaments form numerous end-to-side contacts with other cytoskeletal filaments. Cytochalasin D treatment severely disrupts network organization, increases the number of actin filament ends, and leads to the formation of filamentous aggregates or foci composed mainly of actin filaments. Metabolic inhibitors prevent filament redistribution, foci formation, and cell arborization, but not disorganization of the threedimensional filament network. In cells first extracted and then treated with cytochalasin D, network organization is disrupted, and the number of free filament ends is increased . Supernates of preparations treated in this way contain both short actin filaments and network fragments (i .e ., actin filaments in end-to-side contact with other actin filaments) . It is proposed that the dramatic effects of cytochalasin D on cells result from both a direct interaction of the drug with the actin filament component of cytoskeletal networks and a secondary cellular response . The former leads to an immediate disruption of the ordered cytoskeletal network that appears to involve breaking of actin filaments, rather than inhibition of actin filamentfilament interactions (i .e ., disruption of end-to-side contacts) . The latter engages network fragments in an energy-dependent (contractile) event that leads to the formation of filament foci .The cytochalasins have now been used for more than a decade as tools to study motility-related phenomena in a variety of cell types (e.g., references 7, 11, 26, 27, 39; for an overview, see reference 33) . They exert a number of dramatic morphological effects on cells, including inhibition of ruffling and motility, cell retraction and arborization, zeiosis, blebbing, and enucleation (reviewed in reference 14) . Because of their profound effects on cell morphology and motility, and because of numerous electron microscope observations of marked effects on filamentous structures, it had early been assumed that their primary site of action is the cellular contractile machinery . In fact, cytochalasin-sensitivity alone has often been taken as an indication for the involvement of an actin-based contractile system in certain cellular activities, even in the absence of additional supportive morphological or physiological evidence.However, the mechanism of action of cytochalasin has begun to be understood only recently . In vitro studies using purified

Three-dimensional cytoskeletal organization of detergent-treated epithelial African green monkey kidney cells (BSC-1) and chick embryo fibroblasts was studied in whole-mount preparations visualized in a high voltage electron microscope . Stereo images are generated at both low and high magnification to reveal both overall cytoskeletal morphology and details of the structural continuity of different filament types . By the use of an improved extraction procedure in combination with heavy meromyosin subfragment 1 decoration of actin filaments, several new features of filament organization are revealed that suggest that the cytoskeleton is a highly interconnected structural unit .In addition to actin filaments, intermediate filaments, and microtubules, a new class of filaments of 2-to 3-nm diameter and 30-to 300-nm length that do not bind heavy meromyosin is demonstrated . They form end-to-side contacts with other cytoskeletal filaments, thereby acting as linkers between various fibers, both like (e .g ., actin-actin) and unlike (e .g., actinintermediate filament, intermediate filament-microtubule) . Their nature is unknown . In addition to 2-to 3-nm filaments, actin filaments are demonstrated to form end-to-side contacts with other filaments . Y-shaped actin filament "branches" are observed both in the cell periphery close to ruffles and in more central cell areas also populated by abundant intermediate filaments and microtubules . Arrowhead complexes formed by subfragment 1 decoration of actin filaments point towards the contact site. Actin filaments also form end-to-side contacts with microtubules and intermediate filaments . Careful inspection of numerous actin-microtubule contacts shows that microtubules frequently change their course at sites of contact . A variety of experimentally induced modifications of the frequency of actin-microtubule contacts can be shown to influence the course of microtubules . We conclude that bends in microtubules are imposed by structural interactions with other cytoskeletal elements.A structural and biochemical comparison of whole cells and cytoskeletons demonstrates that the former show a more intricate three-dimensional network and a more complex biochemical composition than the latter . An analysis of the time course of detergent extraction strongly suggests that the cytoskeleton forms a structural backbone with which a large number of proteins of the cytoplasmic ground substance associate in an ordered fashion to form the characteristic image of the "microtrabecular network" (J .