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Dynein Motility: Four Heads Are Better Than Current Biology Vol 15 No 23 R970 and posterior terminal regions are Akam, M., Tautz, D., Denell, R., and (2004). An ancestral role of caudal genes Brown, B. (1996). Class 3 Hox genes in in axis elongation and segmentation. specified differentially. This basic insects and the origin of zen. Proc. Natl. Proc. Natl. Acad. Sci. USA 101, mechanism appears to be Acad. Sci. USA 93, 8479–8484. 17711–17715. instrumental even if the two 5. Schoppmeier, M., and Schröder, R. 12. Miyawaki, K., Mito, T., Sarashina, I., (2005). Maternal Torso-signaling controls Zhang, H., Shinmyo, Y., Ohuchi, H., and terminal regions are specified body axis elongation in a short germ Noji, S. (2004). Involvement of differentially in the same egg and insect. Curr. Biol. 15, this issue. Wingless/Armadillo signaling in the 6. Sommer, R.J., and Tautz, D. (1993). posterior sequential segmentation in the no matter which is the final Involvement of an orthologue of the cricket, Gryllus bimaculatus (Orthoptera), development of those terminal Drosophila pair-rule gene hairy in as revealed by RNAi analysis. Mech. regions in different species. Thus, segment formation of the short germ- Dev. 121, 119–130. band embryo of Tribolium (Coleoptera). 13. van der Zee, M., Berns, N., and And it appears that the Torso pathway Nature 361, 448–450. Roth, S. (2005). Distinct functions of the has been co-opted to match 7. Janody, F., Reischl, J., and Dostatni, N. Tribolium zerknüllt genes in serosa (2000). Persistence of Hunchback in the distinct developmental scenarios. specification and dorsal closure. Curr. terminal region of the Drosophila Biol. 15, 624–636. Now, it remains to be shown blastoderm embryo impairs anterior 14. Doyle, H.J., Kraut, R., and Levine, M. whether Torso signalling is also development. Development 127, (1989). Spatial regulation of zerknüllt: A 1573–1582. dorsal-ventral patterning gene in involved in the development of 8. Casanova, J. (1991). Interaction between Drosophila. Genes Dev. 3, 1518–1533. other short germ animals. torso and dorsal, two elements of 15. Ray, R.P., Arora, K., Nusslein-Volhard, different transduction pathways in the C., and Gelbart, W.M. (1991). The control Drosophila embryo. Mech. Dev. 36, of cell fate along the dorsal-ventral axis References 41–45. of the Drosophila embryo. Development 1. Furriols, M., and Casanova, J. (2003). In 9. Mlodzik, M., and Gehring, W.J. (1987). 113, 35–54. and out of Torso RTK signalling. EMBO Hierarchy of the genetic interactions that J. 22, 1947–1952. specify the anteroposterior segmentation 2. Davis, G.K., and Patel, N.H. (1999). The pattern of the Drosophila embryo as Institut de Biologia Molecular de monitored by caudal protein expression. origin and evolution of segmentation. Barcelona (CSIC), Parc Científic de Trends Cell Biol. 9, M68–M72. Development 101, 421–435. 3. Schröder, R., Eckert, C., Wolff, C., and 10. Weigel, D., Jürgens, G., Klingler, M., and Barcelona, C/Josep Samitier 1-5, 08028 Tautz, D. (2000). Conserved and Jäckle, H. (1990). Two gap genes Barcelona, Spain. divergent aspects of terminal patterning mediate maternal terminal pattern E-mail: [email protected] in the beetle Tribolium castaneum. Proc. formation in Drosophila. Science 248, Natl. Acad. Sci. USA 97, 6591–6596. 495–498. 4. Falciani, F., Hausdorf, B., Schröder, R., 11. Copf, T., Schröder, R., and Averof, M. DOI: 10.1016/j.cub.2005.11.018 Dynein Motility: Four Heads Are dynein-mediated movements in vivo and in vitro is provided by the Better Than Two adaptor molecule dynactin, a very large molecular complex that links dynein to its membrane-based Cytoplasmic dynein is a microtubule-based motor protein that cargos in cells [3]. Work by King transports membranes in cells. The movement driven by a single and Schroer [4] demonstrated that dynein molecule in vitro is not as robust as dynein-driven movements dynactin enhances the processivity in cells. A new study suggests that transport by multiple dyneins is of single dynein molecules to more similar to cellular motions. values measured in cells. Dynactin also has a microtubule-binding James L. McGrath heads spend most of their cycle arm that is essential for enhancing unbound from an actin filament dynein’s processivity [4]. So, by Of the three major types of and so many myosin molecules providing an additional interaction cytoskeletal motors — dyneins, are required to sustain filament with the microtubule rail, dynactin kinesins and myosins — only movement in reconstitution apparently stabilizes the finicky kinesins are strongly processive. assays. Cytoplasmic dynein — a attachment of dynein to a Analysis of single molecule runs minus-end-directed microtubule microtubule. along microtubules show that motor — appears to fall between There is, however, a second kinesins move steadily toward the these extremes. Reconstitution aspect to the in vitro/in vivo plus end of microtubules for studies reveal that short (< 1µm) paradox of dynein motility that is several microns before detaching. minus-end runs are frequently not easily explained by dynactin. Kinesin processivity arises interrupted by pauses and plus- Not only do the dynein-mediated because the two motors of the end motion. So, while dynein movements of organelles proceed dimeric molecule coordinate their molecules can remain attached to over longer distances in cells, but chemical and mechanical cycles microtubules for long periods, these movements also appear to to move ‘hand-over-hand’ and they appear to be processive only be more forceful. Single keep one motor bound to the part of the time. molecules of dynein in vitro stall in microtubule throughout motion. Meanwhile, in living cells, the optical traps at forces of around By contrast, the motor domains of minus-end-directed motions of 1 pN, while the forces required to most dimeric myosins operate organelles along microtubules stall dynein-mediated movements independently (a likely exception often span several microns [1,2]. A in cells can exceed 5 pN [5,6]. is the processive transport sufficient explanation for the Because dynactin is not a motor, specialist myosin V). Myosin difference in processivity between the most reasonable explanation Dispatch R971 is that multiple dynein molecules Figure 1. Cytoskeletal are bound to cellular cargo. This motors have multiple A Kinesin idea led Mallik et al. [7] to examine mechanisms for taking long walks along the motion of artificial cargo filaments. bound to more than one dynein (A) Kinesin is a highly molecule. The group found that processive molecule that the motion of cargo moved by walks hand-over-hand Microtubule multiple dyneins exhibited the remaining in contact with B Myosin persistence and strength of the microtubule through- movements within cells. In fact, out motion. (B) Myosin molecules are disen- Engaged movement by just two dynein gaged throughout most molecules virtually eliminates of their working cycle, backward motions and allows and therefore many Engaged cargo to run four times the myosin molecules are distance seen with a single dynein needed to maintain Actin filament motor. With multiple dyneins and contact during long C One dynein molecule movements. (C) Single dynactin present on cellular dynein molecules are not cargos, retrograde transport in very processive, but they cells is understandably robust. become more processive Most impressive is the clarity when bound to the with which Mallik et al. [7] reveal accessory molecule dyn- the reason that multiple dynein actin, which provides an additional attachment to molecules enhance movement. It the microtubule. (D) The has been known for some time addition of a second that single dynein molecules can dynein molecule to a Microtubule passively diffuse along the length cargo, even in the D Two dynein molecules of microtubules [8,9]. Such absence of dynactin, movements indicate that dynein is allows transport along microtubules for several capable of binding through a microns. weak, non-specific attachment when its motor is inactive. Through a sophisticated separation of the multiple contributions to cargo Microtubule trajectories, Mallik et al. [7] show Current Biology that the diffusive state is a frequent contributor to single dynein movements. In fact, the molecules still advances in 8 nm in response to changes in plus-end movements that step sizes just as when moved by nucleotide states [12]. This, and frequently interrupt minus-end a single dynein molecule. This the fact that the step size of the runs are likely just episodes of suggests that two dynein motor increases at low load, diffusion. The group also shows molecules coordinate their suggests that the central body of that adding resistance to the movements even while both are dynein may function as a cargo motion with an optical trap engaged with a filament. motorized gear box that causes the cargo to slip and to Compared with myosin and transduces the rotation of the diffuse back to the center of trap. kinesin, the operation of the cargo-connected tail to the This indicates that the dynein motor is not well microtubule-connected stalk [13]. microtubule attachments made by understood, but the new One challenge to the idea of the processive dyneins are not very measurements on multi-dynein stalk as a lever is its apparent robust. The low-affinity interaction movement provide some flexibility [12]. However, the data that permits diffusion might be a constraints. The motors of both from Mallik et al. [7] suggest that continuous or regular part of the myosin and kinesin appear to randomly positioned dyneins on a cycle that allows the motor to work as ratchets in which the cargo can step together and that disengage regularly without falling rotation of a cargo-connected structural flexibility might be off its tracks. It is unclear what lever arm is transduced to a step needed for such intermolecular causes the motor to become advancement of the filament- coordination.
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