Dyneins

Certain proteins endow cells with unique capabilities for movement. Cell division, muscle contraction, and cell motility represent some of the ways in which cells execute motion. The contractile and motile proteins underlying these motions share a common property they are filamentous or polymerize to form filaments. Examples include actin and myosin, the filamentous proteins forming the contractile systems of cells, and tubulin, the major component of microtubules (the filaments involved in the mitotic spindle of cell division as well as in flagella and cilia). Another class of proteins involved in movement includes dynein and kinesin, so-called motor proteins that drive the movement of vesicles, granules, and organelles along microtubules serving as established cytoskeletal tracks. ... 

FIGURE 17.5 The structure of an axoneme. Note the manner in which two microtubules are joined in the nine outer pairs. The smaller-diameter tubule of each pair, which is a true cylinder, is called the A-tubule and isjoined to the center sheath of the axoneme by a spoke structure. Each outer pair of tubules isjoined to adjacent pairs by a nexin bridge. The A-tubule of each outer pair possesses an outer dynein arm and an inner dynein arm. The larger-diameter tubule is known as the B-tubule. 

The ability of dyneins to effect mechano-chemical coupling—i.e., motion coupled with a chemical reaction—is also vitally important inside eukaryotic cells, which, as already noted, contain microtubule networks as part of the cytoskele-ton. The mechanisms of intracellular, microtubule-based transport of organelles and vesicles were first elucidated in studies of axons, the long pro-... 

Dyneins Move Organelles in a Plus-to-Minus Direction Kinesins, in a Minus-to-Plus Direction... 

The cytosolic dyneins bear many similarities to axonemal dynein. The protein isolated from C. elegans includes a heavy chain with a molecular mass of approximately 400 kD, as well as smaller peptides with molecular mass ranging from 53 kD to 74 kD. The protein possesses a microtubule-activated ATPase... 

FIGURE 17.7 A mechanism for ciliary motion. The sliding motion of dyneins along one microtnbnle while attached to an adjacent microtnbnle resnlts in a bending motion of the axoneme. 

Motor proteins move along MTs in an ATP-dependent manner. Members of the superfamily of kinesin motors move only to the plus ends and dynein motors only to the minus ends. The respective motor domains are linked via adaptor proteins to their cargoes. The binding activity of the motors to MTs is regulated by kinases and phosphatases. When motors are immobilized at their cargo-binding area, they can move MTs. 

MTs extend from the centrosome throughout the cytoplasm to the plasma membrane, where they are stabilized by caps. Sliding along the MTs, kinesin and dynein motors transport their cargoes between the center and the periphery of the cell. MTs present in the axons of neur ons are extended not only by addition of heterodimers to the plus ends but also by use of short MTs that initiate in the centrosome. Their axonal transport is mediated by dynein motors that are passively moved along actin filaments. Once formed in the axon, MTs serve as tracks for the fast axonal transport, i.e. the movement of membranous organelles and membrane proteins to the nerve ending. 

Some specialized eukaryotic cells have cilia that show a whiplike motion. Sperm cells move with one flagella, which is much longer than a cilium but has a nearly identical internal structure called axoneme. It is composed of nine doublet MTs that form a ring around a pair of single MTs. Numerous proteins bind to the MTs. Ciliary dynein motors generate the force by which MTs slide along each other to cause the bending of the axoneme necessary for motion. 

The membrane tubules and lamellae of the endoplasmic reticulum (ER) are extended in the cell with the use of MTs and actin filaments. Kinesin motors are required for stretching out the ER, whereas depolymerization of microtubules causes the retraction of the ER to the cell centre in an actin-dependent manner. Newly synthesized proteins in the ER are moved by dynein motors along MTs to the Golgi complex (GC), where they are modified and packaged. The resulting vesicles move along the MTs to the cell periphery transported by kinesin motors. MTs determine the shape and the position also of the GC. Their depolymerization causes the fragmentation and dispersal of the GC. Dynein motors are required to rebuild the GC. 

In view of the importance of the motor dynein for microtubular function, this protein is currently considered as a new target for the development of cytostatic agents. 

The force-producing MAPs (kinesin, dynein, and dynamin) function as energy-transducing ATPases to provide the motive force for cilia and flagella by means of... 

Both dynein and MAP2 interact with microtubules at the same binding sites, namely, the C termini of a- and p-tubulin. Also, MAP2 inhibits the microtubule-activated ATPase of dynein and prevents microtubule gliding on dynein-coated glass coverslips. Thus, MAP2 and other fibrous MAPs may be regulators of microtubule-based motility in vivo (Paschal et al., 1989). 

The axoneme consists of a cylinder of nine outer doublets of fused microtubules and a pair of discrete central microtubules (commonly referred to as the 9 + 2 arrangement of microtubules). The outer doublets each consist of a complete A-microtubule and an incomplete B-microtubule, the deficiency in the wall of the latter being made up by a sharing of wall material with the former. The tip of the axoneme contains the plus ends of all of the constituent microtubules. Two curved sidearms, composed of the MAP protein dynein, are attached at regular intervals to the A-microtubules of each fused outer doublet (Figures 1 and 2). 

Dynein sidearms interact with the walls of B-microtubules of adjacent doublets by means of a sliding-filament mechanism to produce ciliary movement. The process is energized by ATP hydrolysis. Movement of the cilium occurs in two stages, termed the power stroke and the recovery stroke. 

Figure 2. Electron micrograph of cross section of flagellum of mouse sperm, taken near the tip. The axoneme contains nine outer pairs of doublet microtubules and two central singlet microtubules. Several dynein arms and the fibrous sheath of the sperm are also shown.

An isolated flagellum will continue to bend actively, indicating that this function is linked to its intrinsic structure. Treatment of cilia from the protozoan Tetra-hymena with the proteolytic enzyme trypsin selectively dissolves the nexin links and radial spokes but leaves unaffected the microtubules and dynein arms. If such a preparation is treated with a small amount of ATP, the loosened microtubule doublets slide against each other and through longitudinal overlap, extend for a distance that is up to nine times the original length of the cilium (Warner and Mitchell, 1981). 

Dynein, kinesin, and myosin are motor proteins with ATPase activity that convert the chemical bond energy released by ATP hydrolysis into mechanical work. Each motor molecule reacts cyclically with a polymerized cytoskeletal filament in this chemomechanical transduction process. The motor protein first binds to the filament and then undergoes a conformational change that produces an increment of movement, known as the power stroke. The motor protein then releases its hold on the filament before reattaching at a new site to begin another cycle. Events in the mechanical cycle are believed to depend on intermediate steps in the ATPase cycle. Cytoplasmic dynein and kinesin walk (albeit in opposite... 

Even though dynein, kinesin, and myosin serve similar ATPase-dependent chemomechanical functions and have structural similarities, they do not appear to be related to each other in molecular terms. Their similarity lies in the overall shape of the molecule, which is composed of a pair of globular heads that bind microtubules and a fan-shaped tail piece (not present in myosin) that is suspected to carry the attachment site for membranous vesicles and other cytoplasmic components transported by MT. The cytoplasmic and axonemal dyneins are similar in structure (Hirokawa et al., 1989 Holzbaur and Vallee, 1994). Current studies on mutant phenotypes are likely to lead to a better understanding of the cellular roles of molecular motor proteins and their mechanisms of action (Endow and Titus, 1992). 

Amos, L.A. (1989). Brain dynein crossbridges microtubules into bundles. J. Cell Sci. 93, 19-28. Amos, L.A. (1995). The microtubule lattice— 20 years on. Trends Cell Biol. 5,48-51. 

Asai, D.J. Brokaw, C.J. (1993). Dynein heavy chain isoforms and axonemal motility. Trends Cell Biol. 3. 398-402. 

Gibbons, l.R. (1988). Dynein ATPases as microtubule motors. J. Biol. Chem. 263, 15837-15840. 

Holzbaur, E.L.F. Vallee, R.B. (1994). Dyneins Molecular structure and cellular function. Ann. Rev. Cell Biol. 10,339-372. 

Paschal, B.M., Shpetner, H.S., Vallee, R.B. (1987). MAP IC is a microtubule-activated ATPase which translocates microtubules in vitro and has dynein-like properties. J. Cell Biol. 105, 1273-1282. 

Paschal, B.M., Obar, R.A., Vallee, R.B. (1989). Interaction of brain cytoplasmic dynein and MAP2 with a common sequence at the C terminus of tubulin. Namre 342, 569-572. 

Schroer, T.A. (1994). Structure, function and regulation of cytoplasmic dynein. Curr. Opin. Cell Biol. 

Warner, F.D. Mitchell, D.R. (1981). Polarity of dynein-microtubule interactions in vitro Cross-bridging between parallel and antiparallel microtubules. J. Cell Biol. 89, 35-44. 

Figure 6. Transport of material along the nerve axon. Materials such as neurotransmitter peptides are synthesized in the cell body and sequestered in vesicles at the Golgi. Vesicles are then transported down the axon towards the synapse by kinesin motors. Other materials are transported from the synapse to the cell body by dynein motors.

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