BBA - Molecular Cell Research (v.1496, #1)
by George S Bloom (1-2).
Myosins: a diverse superfamily by James R Sellers (3-22).
Myosins constitute a large superfamily of actin-dependent molecular motors. Phylogenetic analysis currently places myosins into 15 classes. The conventional myosins which form filaments in muscle and non-muscle cells form class II. There has been extensive characterization of these myosins and much is known about their function. With the exception of class I and class V myosins, little is known about the structure, enzymatic properties, intracellular localization and physiology of most unconventional myosin classes. This review will focus on myosins from class IV, VI, VII, VIII, X, XI, XII, XIII, XIV and XV. In addition, the function of myosin II in non-muscle cells will also be discussed.
Keywords: Myosin II; Myosin IV; Myosin VI–VIII; Myosin X–XV;
Regulation of the enzymatic and motor activities of myosin I by Barbara Barylko; Derk D. Binns; Joseph P. Albanesi (23-35).
Myosins I were the first unconventional myosins to be purified and they remain the best characterized. They have been implicated in various motile processes, including organelle translocation, ion channel gating and cytoskeletal reorganization but their exact cellular functions are still unclear. All members of the myosin I family, from yeast to man, have three structural domains: a catalytic head domain that binds ATP and actin; a tail domain believed to be involved in targeting the myosins to specific subcellular locations and a junction or neck domain that connects them and interacts with light chains. In this review we discuss how each of these three domains contributes to the regulation of myosin I enzymatic activity, motor activity and subcellular localization.
Keywords: Unconventional myosin; Phosphorylation; Isoleucine–glutamine (IQ) domain;
Class V myosins by Samara L Reck-Peterson; D.William Provance; Mark S Mooseker; John A Mercer (36-51).
Keywords: Myosin V; Unconventional myosin; mRNA transport; Membrane traffic; Vacuolar inheritance;
Are class III and class IX myosins motorized signalling molecules? by Martin Bähler (52-59).
Myosins exist that are fused to domains that harbour signalling activities. Class III myosins (NINAC) are protein kinases that play important roles in phototransduction. Class IX myosins inactivate the small G-protein Rho that acts as molecular switch. Because these myosins interact via their myosin head domain with actin filaments, they link signal transduction to the actin cytoskeleton. The exact motor properties of these myosins, however, remain to be determined.
Keywords: Myosin III; Myosin IX; Protein kinase; Rho; Motor molecule; Actin; Calmodulin; Photoreception;
The dynein microtubule motor by Stephen M King (60-75).
Dyneins are large multi-component microtubule-based molecular motors involved in many fundamental cellular processes including vesicular transport, mitosis and ciliary/flagellar beating. In order to achieve useful work, these enzymes must contain motor, cargo-binding and regulatory components. The ATPase and microtubule motor domains are located within the very large dynein heavy chains that form the globular heads and stems of the complex. Cargo-binding activity involves the intermediate chains and several classes of light chain that associate in a subcomplex at the base of the soluble dynein particle. Regulatory control of dynein motor function is thought to involve the phosphorylation of various components as well as a series of light chain proteins that are directly associated with the heavy chains. These latter polypeptides have a variety of intriguing attributes, including redox-sensitive vicinal dithiols and Ca2+-binding, suggesting that the activity of individual dyneins may be subject to multiple regulatory inputs. Recent molecular, genetic and structural studies have revealed insight into the roles played by these various components and the mechanisms of dynein-based motility.
Keywords: Cilia; Dynein; Flagella; Microtubule; Motility;
Distinct cytoplasmic dynein complexes are transported by different mechanisms in axons by S.J. Susalka; W.O. Hancock; K.K. Pfister (76-88).
In neurons, cytoplasmic dynein is synthesized in the cell body, but its function is to move cargo from the axon back to the cell body. Dynein must therefore be delivered to the axon and its motor activity must be regulated during axonal transport. Cytoplasmic dynein is a large protein complex composed of a number of different subunits. The dynein heavy chains contain the motor domains and the intermediate chains are involved in binding the complex to cargo. Five different intermediate chain polypeptides, which are the result of the alternative splicing of the two intermediate chain genes, have been identified. We have characterized two distinct pools of dynein that are transported from the cell body along the axon by different mechanisms. One pool, which contains the ubiquitous intermediate chain, is associated with the membranous organelles transported by kinesin in the fast transport component. The other pool, which contains the other developmentally regulated intermediate chains, is transported in slow component b. The mechanism of dynein regulation will therefore depend on which pool of dynein is recruited to function as the retrograde motor. In addition, the properties of the large pool of dynein associated with actin in slow component b are consistent with the hypothesis that this dynein may be the motor for microtubule transport in the axon.
Keywords: Cytoplasmic dynein; Axonal transport; Cytoskeleton; Motor protein; Microtubule;
The role of cytoplasmic dynein in the human brain developmental disease lissencephaly by Richard B Vallee; Nicole E Faulkner; Chin-Yin Tai (89-98).
Lissencephaly is a brain developmental disorder characterized by disorganization of the cortical regions resulting from defects in neuronal migration. Recent evidence has implicated the human LIS-1 gene in Miller–Dieker lissencephaly and isolated lissencephaly sequence. LIS-1 is homologous to the fungal genes NudF and PAC1, which are involved in cytoplasmic dynein mediated nuclear transport, but it is also almost identical to a subunit of PAF acetylhydrolase, an enzyme which inactivates the lipid mediator platelet activating factor. Recent evidence from our laboratory has revealed that cytoplasmic dynein coimmunoprecipitates with LIS-1 in bovine brain cytosol, supporting a role in the dynein pathway in vertebrates. Overexpression of LIS-1 interferes with cell division, with noteworthy effects on chromosome attachment to the mitotic spindle and on the interaction of astral microtubules with the cell cortex. Other aspects of dynein function, such as the organization of the Golgi apparatus, are not affected. Together, these results suggest a role for LIS-1 in cytoplasmic dynein functions involving microtubule plus-ends. Furthermore, they suggest that mutations in LIS-1 may produce a lissencephalic phenotype either by interfering with the movement of neuronal nuclei within extending processes, or by interference with the division cycle of neuronal progenitor cells in the ventricular and subventricular zones of the developing nervous system.
Keywords: Microtubule; Cytoplasmic dynein; Lissencephaly; Mitosis; Neuronal migration; Brain development;
Mitotic motors in Saccharomyces cerevisiae by Emily R Hildebrandt; M.Andrew Hoyt (99-116).
The budding yeast Saccharomyces cerevisiae provides a unique opportunity for study of the microtubule-based motor proteins that participate in mitotic spindle function. The genome of Saccharomyces encodes a relatively small and genetically tractable set of microtubule-based motor proteins. The single cytoplasmic dynein and five of the six kinesin-related proteins encoded have been implicated in mitotic spindle function. Each motor protein is unique in amino acid sequence. On account of functional overlap, no single motor is uniquely required for cell viability, however. The ability to create and analyze multiple mutants has allowed experimental dissection of the roles performed by each mitotic motor. Some of the motors operate within the nucleus to assemble and elongate the bipolar spindle (kinesin-related Cin8p, Kip1p, Kip3p and Kar3p). Others operate on the cytoplasmic microtubules to effect spindle and nuclear positioning within the cell (dynein and kinesin-related Kip2p, Kip3p and Kar3p). The six motors apparently contribute three fundamental activities to spindle function: motility, microtubule cross-linking and regulation of microtubule dynamics.
Keywords: Kinesin; Dynein; Mitosis; Spindle; Microtubule; Saccharomyces cerevisiae;
Directional motility of kinesin motor proteins by Günther Woehlke; Manfred Schliwa (117-127).
Kinesin motor proteins are molecules capable of moving along microtubules. They share homology in the so-called core motor domain which acts as a microtubule-dependent ATPase. The surprising finding that different members of the superfamily move in opposite directions along microtubules despite their close similarity has stimulated intensive research on the determinants of motor directionality. This article reviews recent biophysical, biochemical, structural and mutagenic studies that contributed to the elucidation of the mechanisms that cause directional motion of kinesin motor proteins.
Keywords: Molecular motor; Kinesin; Non-claret disjunctional protein; Directionality; Processivity; Microtubule;
Roles of motor proteins in building microtubule-based structures: a basic principle of cellular design by David J Sharp; Gregory C Rogers; Jonathan M Scholey (128-141).
Eukaryotic cells must build a complex infrastructure of microtubules (MTs) and associated proteins to carry out a variety of functions. A growing body of evidence indicates that a major function of MT-associated motor proteins is to assemble and maintain this infrastructure. In this context, we examine the mechanisms utilized by motors to construct the arrays of MTs and associated proteins contained within the mitotic spindle, neuronal processes, and ciliary axonemes. We focus on the capacity of motors to drive the ‘sliding filament mechanism’ that is involved in the construction and maintenance of spindles, axons and dendrites, and on a type of particle transport called ‘intraflagellar transport’ which contributes to the assembly and maintenance of axonemes.
Keywords: Microtubule; Motor protein; Kinesin; Dynein; Polarity pattern; Axon; Dendrite; Spindle; Axoneme;
Understanding the functions of kinesin-II by Joseph R. Marszalek; Lawrence S.B. Goldstein (142-150).
Species ranging from Chlamydomonas to humans possess the heterotrimeric kinesin-II holoenzyme composed of two different motor subunits and one non-motor accessory subunit. An important function of kinesin-II is that it transports the components needed for the construction and maintenance of cilia and flagella from the site of synthesis in the cell body to the site of growth at the distal tip. Recent work suggests that kinesin-II does not directly interact with these components, but rather via a large protein complex, which has been termed a raft (intraflagellar transport (IFT)). While ciliary transport is the best-established function for kinesin-II, evidence has been reported for possible roles in neuronal transport, melanosome transport, the secretory pathway and during mitosis.
Keywords: Kinesin-II; Kinesin; Microtubule transport; Raft; Cilia transport;