Unconventional myosins: new frontiers in actin-based motors

The unconventional myosins are a superfamily of actin-based motors responsible for a rich array of intracellular motility events. Recent evidence suggests that these motors play important roles in cell migration, endocytosis and intracellular transport. Several genetic mutants have been identified whose abnormalities are the result of the loss of a specific myosin. This article describes how analysis of these mutants, coupled with basic studies of the intracellular localization and biochemical properties of individual myosins, is leading to a clearer understanding of the in vivo function of a number of these interesting motor proteins.     

Unconventional myosins: anchors in the membrane traffic relay

The family of unconventional myosins is ever growing and the functions attributed to them seem to expand in parallel. These actin-based motor proteins have been implicated in processes as seemingly diverse as endocytosis and exocytosis, the transport of organelles, in spermatogenesis and in neurosensory functions such as hearing and sight. A common myosin function may underlie them all — the regulation of intracellular membrane traffic.     

Unconventional myosins at the crossroad of signal transduction and cytoskeleton remodeling

The cytoplasm of eukaryotic cells is a complex milieu and unraveling how its unique cytoarchitecture is achieved and maintained is a central theme in modern cell biology. The actin cytoskeleton is essential for the maintenance of cell shape and locomotion, and also provides tracks for active intracellular transport. Myosins, the actin-dependent motor proteins form a superfamily of at least 15 structural classes and have been identified in a wide variety of organisms, making the presence of actin and myosins a hallmark feature of eukaryotes. Direct connections of myosins to a variety of cellular tasks are now emerging, such as in cytokinesis, phagocytosis, endocytosis, polarized secretion and exocytosis, axonal transport. Recent studies reveal that myosins also play an essential role in many aspects of signal transduction and neurosensation.     

Unconventional myosins at the crossroad of signal transduction and cytoskeleton remodeling

Summary The cytoplasm of eukaryotic cells is a complex milieu and unraveling how its unique cytoarchitecture is achieved and maintained is a central theme in modern cell biology. The actin cytoskeleton is essential for the maintenance of cell shape and locomotion, and also provides tracks for active intracellular transport. Myosins, the actin-dependent motor proteins form a superfamily of at least 15 structural classes and have been identified in a wide variety of organisms, making the presence of actin and myosins a hallmark feature of eukaryotes. Direct connections of myosins to a variety of cellular tasks are now emerging, such as in cytokinesis, phagocytosis, endocytosis, polarized secretion and exocytosis, axonal transport. Recent studies reveal that myosins also play an essential role in many aspects of signal transduction and neurosensation.     

Peroxidative crosslinking of myosins.

The effect of myoglobin, free hemin and H2O2 on myosins from heart and skeletal muscle was studied. SDS-gel electrophoresis revealed that each agent caused intermolecular thiol crosslinking of both myosins dissociable by excess of beta-mercaptoethanol. In the simultaneous presence of H2O2 and myoglobin or H2O2 and free hemin, myosin formed covalent aggregates undissociable by beta-mercaptoethanol and therefore assessed to formation of non S-S inter molecular covalent bonds. The latter aggregates are suggested to result from pairing of myosin radicals formed by the H2O2 induced ferryl iron state in myoglobin, free hemin or hemo-myosin.     

Axonal myosins

Brain Cell Biology - The myosin super family is an extended family of actin-based motor proteins that can be divided into 15–18 structurally distinct classes (Sellers, J. R (2000) Biochemica...     

Predicting allosteric switches in myosins.

The sequences of several members of the myosin family of molecular motors are evaluated using ASP (Ambivalent Structure Predictor), a new computational method. ASP predicts structurally ambivalent sequence elements by analyzing the output from a secondary structure prediction algorithm. These ambivalent sequence elements form secondary structures that are hypothesized to function as switches by undergoing conformational rearrangement. For chicken skeletal muscle myosin, 13 discrete structurally ambivalent sequence elements are identified. All 13 are located in the heavy chain motor domain. When these sequence elements are mapped into the myosin tertiary structure, they form two compact regions that connect the actin binding site to the adenosine 5'-triphosphate (ATP) site, and the ATP site to the fulcrum site for the force-producing bending of the motor domain. These regions, predicted by the new algorithm to undergo conformational rearrangements, include the published known and putative switches of the myosin motor domain, and they form plausible allosteric connections between the three main functional sites of myosin. The sequences of several other members of the myosin I and II families are also analyzed.     

Regulatory light chains in myosins.

Scallop myosin molecules contain two moles of regulatory light chains and two moles of light chains with unknown function. Removal of one of the regulatory light chains by treatment with EDTA is accompanied by the complete loss of the calcium dependence of the actin-activated ATPase activity and by the loss of one of the two calcium binding sites on the intact molecule. Such desensitized preparations recombine with one mole of regulatory light chain and regain calcium regulation and calcium binding. The second regulatory light chain may be selectively obtained from EDTA-treated scallop muscles by treatment with the Ellman reagent (5,5′-dithiobis(2-nitrobenzoic acid)): treatment with this reagent, however, leads to an irreversible loss of ATPase activity. The light chains obtained by treatment with EDTA and then DTNB are identical in composition and function. A different light chain fraction obtained by subsequent treatment with guanidine-HCl does not bind to desensitized or intact myoflbrils and has no effect on ATPase activity.Regulatory light chains which bind to desensitized scallop myofibrils with high affinity and restore calcium control were found in a number of molluscan and vertebrate myosins, including Mercenaria, Spisula, squid, lobster tail, beef heart, chicken gizzard, frog and rabbit. Although these myosins all have a similar subunit structure and contain about two moles of regulatory light chain, only scallop myosin or myofibrils can be desensitized by treatment with EDTA.There appear to be two classes of regulatory light chains. The regulatory light chains of molluscs and of vertebrate smooth muscles restore full calcium binding and also resensitize purified scallop myosin. The regulatory light chains from vertebrate striated, cardiac, and the fast decapod muscles, on the other hand, have no effect on calcium binding and do not resensitize purified scallop myosin unless the myosin is complexed with actin. The latter class of light chains is found in muscles where in vitro functional tests failed to detect myosin-linked regulation.     

Novel myosins

The traditional view of myosin, drawn from studies of myosins from striated muscles, is that of an elongated two-headed molecule that assembles into filaments. However, biochemical, molecular genetic and genetic studies have uncovered a host of ubiquitous single-headed nonfilamentous myosins known collectively as myosins I. All of the myosins I possess the myosin head domain, the motor portion of muscle myosins they have tail the filament-forming tail domain of muscle myosins they have tail domains that interact variously with membranes, actin and calmodulin. These alternative molecular interactions confer novel motile properties on myosins I, such as the ability to move membranes relative to actin and to move actin relative to actin without having to assemble into filaments. The numerous actin-based movements retained by cells lacking myosin II, the two-headed filamentous form of nonmuscle myosin, may be supported by myosins I.     

Plant myosins

Summary Plant myosins are motor proteins that bind to the external surfaces of organelles and interact with the cytoskeletal protein actin (as actin microfilaments), which organizes and directs intracellular movement. Recent progress in physiological, biochemical, immunological, and genetical studies of plant myosin has revealed considerable information about the structures and functions of these important molecules. This article briefly reviews the history of plant myosin research, summarizes recent progress, and highlights directions for future research. Dedicated to the memory of the late Professor Noburo Kamiya (1913–1999)     

Unconventional cancer remedies.

Unproven and disproven remedies continue to abound for illnesses for which conventional treatment is only partially effective. This is particularly true with cancer, for which up to 50% of patients may be receiving unorthodox therapy. This article examines unconventional cancer remedies, their adverse effects, their common factors and the basis for their appeal, as well as what motivates and characterizes patients who choose these treatments. Also discussed is an approach that may be used by the conventional physician for patients who are likely to seek unorthodox treatment. This approach will help patients make the best decision about their treatment and protect them from the hazards of unconventional remedies.     

Assembly of cytoplasmic and smooth muscle myosins.

Filaments formed from a variety of smooth and non-muscle myosins are dynamic polymers whose phosphorylation-dependent assembly and disassembly can be coupled to changes in enzymatic activity. Phosphorylation-insensitive assembly, which allows independent control of activity and polymerization, is an alternative mechanism used by Acanthamoeba myosin. Domains of the tail responsible for assembly and regulation have now been identified for a number of myosins.     

Regulation of calmodulin-binding myosins

Myosins constitute a diverse superfamily of actin-based mechanoenzymes that are involved in many essential cellular motilities. In addition to conventional muscle myosin II, ten other classes of unconventional myosins are known. Many unconventional myosins bind multiple calmodulin light chains and Ca2+, which can dramatically alter their mechanochemical and enzymatic activity. Calmodulin-binding myosins can also be regulated by phospholipid binding, phosphorylation of the heavy chain and actin-binding proteins. The molecular details linking unconventional-myosin regulation and function are just beginning to emerge.