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5. McMahon, T.A., and Cheng, G.C. (1990). The 9. Full, R.J., and Koditschek, D.E. (1999). implications for energy cost. J. Appl. Physiol. mechanics of running: How does stiffness Templates and Anchors: Neuromechanical 97, 2266–2274. couple with speed? J. Biomech. 23, 65–78. hypotheses of legged locomotion on land. 14. McGeer, T. (1993). Dynamics and control of 6. Raibert, M.H., Chepponis, M., and Brown, H. J. Exp. Biol. 202, 3325–3332. bipedal locomotion. J. Theor. Biol. 163, (1986). Running on four legs as though they 10. Seyfarth, A., Geyer, H., and Herr, H. (2003). 277–314. were one. IEEE J. Robotics Automation 2, Swing-leg retraction: a simple control model 15. Muybridge, E. (1887). Muybridge’s Complete 70–82. for stable running. J. Exp. Biol. 206, 2547–2555. Human and Animal Locomotion (Courier Dover 7. Altendorfer, R., Moore, N., Komsuolu, H., 11. Daley, M.A., and Biewener, A.A. (2006). Running Publications). Buehler, M., Brown, H.B., McMordie, D., over rough terrain reveals limb control for Saranli, U., Full, R., and Koditschek, D.E. intrinsic stability. Proc. Natl. Acad. Sci. USA (2001). RHex: A biologically inspired 103, 15681–15686. The Royal Veterinary College, Hawkshead hexapod runner. Autonomous Robots 11, 12. Moritz, C.T., and Farley, C.T. (2004). Passive Lane, North Mymms, Hatfield, Hertfordshire 207–213. dynamics change leg mechanics for an AL9 7TA, UK. 8. Pollock, C.M., and Shadwick, R.E. (1994). unexpected surface during human hopping. E-mail: [email protected] Allometry of muscle, tendon, and elastic energy J. Appl. Physiol. 97, 1313–1322. storage capacity in mammals. Am. J. Physiol. 13. Biewener, A.A., Farley, C.T., Roberts, T.J., and Regul. Integr. Comp. Physiol. 266, Temaner, M. (2004). Muscle mechanical R1022–R1031. advantage of human walking and running: DOI: 10.1016/j.cub.2008.09.050

Organelle Transport: Dynamic actin transport track as the moves [5] (Figure 1B). Tracks for Myosin Motors Extension of actin transport tracks during organelle motility explains an apparent paradox in pigment granule Transport of cargo by molecular motors on and actin filament movement on actin. The length of tracks is a fundamental property of eukaryotic cells. A new study reports individual actin filaments associated that actin dynamics are required in cells for myosin I and V motor to with pigment granules is short, ranging transport their organelle cargos on actin tracks. from 0.2 to 3 mm for the majority of filaments, with an average of 1.3 mm Louise Cramer respectively, along actin tracks [8,9], yet individual pigment granules in frog pigment cells (known as are transported by myosin V on actin Transport of cargo inside cells was melanophores). The term ‘actin tracks over far greater total distances a landmark discovery over 200 years dynamics’ in this context means that (from 3 to >10 mm) [5,9]. One ago [1]. Intracellular transport is individual actin filaments are rapidly reasonable explanation of this essential for and a variety of polymerizing and depolymerizing. paradox, with no a priori requirement cargo is transported — membrane- Actin and microtubule dynamics are for actin dynamics, is that myosin V bound organelles, such as the already known to be important for other motors switch between static actin nucleus, Golgi, secretory and distinct types of cargo transportation, tracks to increase the total distance endocytic vesicles, as well as such as cargo surfing on the ends of moved by an individual cargo. non-membrane-bound particles such polymerizing , or actin- However, switching of static tracks is as mRNA, and proteins involved in polymerization-mediated rocketing of not favoured because insufficient signalling and establishing polarity. some and bacterial/viral tracks touch individual organelles [5], In addition, some bacteria and viruses pathogens (Figure 1A). In rocketing and this switching is also not favoured subvert intracellular cargo transport motility, actin dynamics are important in a mathematical model [8]. The systems to infect human and other because actin polymerization is revelation that the actin transport animal cells and to cause disease. directly coupled to providing the force tracks are dynamic [5] adds a new The most widely used system for that drives the movement of the dimension, allowing dynamic extension transporting cargo in eukaryotic cells is or pathogen forwards of actin transport tracks during myosin- directed movement driven by (Figure 1A). However, it is less V-based organelle motility to be molecular motors moving along immediately obvious why actin a rational solution to the paradox transport tracks made of cytoskeletal dynamics should be important for (Figure 1B). Conceivably, actin polymers — and motors myosin-mediated transport of dynamics can extend the total journey are required for movement along and pigment granules an individual pigment granule makes in microtubule tracks [2] and for where, in contrast to rocketing motility, two ways. One is a simple extension of movement along actin filament tracks actin filaments are already polymerized the same track the organelle is moving [3,4]. The expectation is that these before transportation is needed and on (Figure 1B, actin track 1) and the types of transport track are relatively simply provide actin substrate for other is by bridging to a nearby, but stable so that they can support useful myosin to move on (Figure 1B). The not directly touching, second actin cargo movement. It is perhaps authors experimentally exclude the track (Figure 1B, actin track 2), surprising then that new experimental possibility that actin dynamics are although neither scenario has yet been findings [5], reported in a recent issue needed to create spatial openings in directly visualized in cells. Bridging to of Current Biology, show that the the actin meshwork to provide access a nearby actin track of different spatial myosin class I [6] and V [7] motors need for organelle transport on separate orientation in the cell could account actin dynamics to pull their cargo of actin tracks. The likely answer is that for the abrupt directional changes in lysosomes and pigment granules, actin dynamics allow extension of the movement that individual pigment Dispatch R1067

actin filaments within lamellipodial or A B filopodial membrane protrusions at the cell periphery (half-life of 1–2 minutes). Significantly, myosin I motors in yeast directly stimulate actin dynamics during [14–18]. This offers the new, though yet unexplored 1 possibility that myosin transport 2 motors like myosin I and V directly stimulate actin polymerization or depolymerization when pulling their cargo on actin tracks, resulting in the extension of their own track for their

Current Biology own further advancement.

References Figure 1. Actin dynamics and organelle transport. 1. Kuroda, K. (1990). Cytoplasmic streaming in The distinct types of actin-based organelle and particle transport present in cells differ in the plants. Int. Rev. Cytol. 121, 267–307. source of power to move the organelle/particle [19,20]. Two common distinct types of actin- 2. Vale, R.D. (2003). The tool based transport require actin dynamics for different purposes. (A) In rocketing motility, poly- box for intracellular transport. Cell 112, 467–480. merization (curved on-arrow) of actin monomer (single pink chevron) between the organelle/ 3. Tuxworth, R.I., and Titus, M.A. (2000). particle cargo (orange sphere) and associated actin filament (chevrons) directly powers for- Unconventional myosins: anchors in the ward movement of cargo. (B) In myosin-driven transport, myosin I and V motors (black stick membrane traffic relay. Traffic 1, 11–18. and ball) pull organelle/particle cargo (green sphere) along a preformed track of actin filaments 4. Krendel, M., and Mooseker, M.S. (2005). (chevrons) towards only one end of the track (for these two motors, the barbed, or plus end). Myosins: tails (and heads) of functional diversity. Physiol. 20, 239–251. During pigment granule and transport in melanophores [5], ongoing actin polymer- 5. Semenova, I., Burakov, A., Berardone, N., ization (curved on-arrow) either simply extends the original actin track (1), and/or bridges the Zaliapin, I., Slepchenko, B., Svitkina, T.M., original actin track (1) to the next actin track (2); in both cases, the total distance that an indi- Kashina, A., and Rodionov, V. (2008). Actin vidual organelle travels on actin is increased. For these organelles, the measured net organelle dynamics is essential for myosin-based displacement on actin is shorter than the measured total distance travelled [5,9] due to the transport of membrane organelles. Curr. Biol. 18, 1581–1586. known random arrangement of actin-tracks (compare straight arrows) [5,9]. In cells, for both 6. Cordonnier, M.-N., Dauzonne, D., Louvard, D., rocketing transport of cargo [10] and myosin-driven organelle transport [5], actin filament and Coudrier, E. (2001). Actin filaments and depolymerization (curved off-arrow), rather than desequestration of stored actin monomer myosin I alpha cooperate with microtubules for (chevron in a box), at least in part directly provides the required actin monomer (single pink the movement of lysosomes. Mol. Biol. Cell 12, chevron) to fuel ongoing actin polymerization. 4013–4029. 7. Rogers, S.L., and Gelfand, V.I. (1998). Myosin cooperates with microtubule motors during granules make on actin tracks [5,9] migration [10] — that are directly organelle transport in melanophores. Curr. Biol. (Figure 1B, the direction of travel of regulated by controlling actin 8, 161–163. 8. Snider, J., Lin, F., Zahedi, N., Rodionov, V.I., individual cargo changes when actin depolymerization and recycling. This Yu, C.C., and Gross, S.P. (2004). Intracellular track 1 bridges to actin track 2). may also explain the known actin-based transport: How far you go depends on how often you switch. Proc. Natl. Acad. Sci. There are several important requirement for ADF/cofilin, a family of 101, 13204–13209. implications of the dynamic extension proteins that sever and depolymerize 9. Rodionov, V.I., Hope, A.J., Svitkina, T.M., and of actin transport tracks in cells. For actin filaments, in the transport of Borisy, G.G. (1998). Functional coordination of microtubule-based and actin-based motility in example, what is the cellular origin of Golgi-derived secretory vesicles in melanophores. Curr. Biol. 8, 165–168. the actin monomers required to extend cells [11]. 10. Cramer, L.P. (1999). Role of actin-filament disassembly in lamellipodium protrusion the actin filament track? Knowing the Another implication of the new data in motile cells revealed using the drug answer to this question is important is that actin dynamics are likely to be jasplakinolide. Curr. Biol. 9, 1095–1105. as it predicts candidate regulatory stimulated during myosin-V-based 11. Rosso, S., Bollati, F., Bisbal, M., Peretti, D., Sumi, T., Nakamura, T., Quiroga, S., Ferreira, A., molecules involved. Direct inhibition transport of pigment granules and and Caceres, A. (2004). LIMK1 regulates Golgi of actin-filament depolymerization in myosin-I-based transport of dynamics, traffic of Golgi-derived vesicles, and process extension in primary cultured neurons. melanophores reduces the transport of lysosomes on actin tracks. Actin tracks Mol. Biol. Cell 15, 3433–3449. pigment granules and lysosomes [5]. for myosin-driven movement of these 12. Hotulainen, P., and Lappalainen, P. (2006). This argues that at least a proportion of organelles in melanophores are located Stress fibers are generated by two distinct actin assembly mechanisms in motile cells. J. Cell the actin monomers required to extend throughout the cytoplasm within the Biol. 173, 383–394. the actin tracks must come directly cell body [5,9]. One measure of actin 13. Cramer, L.P., Siebert, M., and Mitchison, T.J. (1997). Identification of novel graded polarity from actin depolymerization and dynamics is the rate of actin filament actin filament bundles in locomoting heart recycling (Figure 1B, single chevron), turnover and the measured half-life for fibroblasts: implications for the generation of rather than from the alternative known actin transport tracks in the cell body of motile force. J. Cell Biol. 136, 1287–1305. 14. Evangelista, M., Klebl, B.M., Tong, A.H.Y., supply of de-sequestration of stored melanophores (2 minutes) [5] is much Webb, B.A., Leeuw, T., Leberer, E., monomer (Figure 1B, chevron in a box). shorter than that expected for actin Whiteway, M., Thomas, D.Y., and Boone, C. (2000). A role for myosin-I in actin assembly Organelle transport on actin filaments filaments in this region of the cell through interactions with Vrp1p, Bee1p, and driven by myosin motors [5] therefore (half-life of 5–10 minutes [12,13]). the Arp2/3 complex. J. Cell Biol. 148, 353–362. adds to the growing list of distinct Although this could simply reflect 15. Lechler, T., Shevchenko, A., Shevchenko, A., and Li, R. (2000). Dierct involvement of yeast types of motility in cells — including a difference in cell type or function, type I myosins in Cdc42-dependent actin propulsion of pathogenic bacteria the rate of turnover of actin transport polymerization. J. Cell Biol. 148, 363–373. 16. Lee, W.-L., Bezanilla, M., and Pollard, T.D. (Figure 1A) [10] and protrusion of the tracks in the cell body of melanophores (2000). Fission yeast myosin-I, Myo1p, leading cell margin during cell is much closer to that of highly dynamic stimulates assembly by Arp2/3 complex and Current Biology Vol 18 No 22 R1068

shares functions with WASp. J. Cell Biol. 151, requires coordinated actin nucleation and MRC-Laboratory Molecular Cell Biology/Cell 789–799. myosin motor activity. Dev. Cell 11, 33–46. Biology Unit and Department of Cell and 17. Sirotkin, V., Beltzner, C.C., Marchand, J.-B., 19. Cramer, L.P. (1997). Molecular mechanism of Developmental Biology, University College and Pollard, T.D. (2005). Interactions of WASp, actin-dependent retograde flow in lamellipodia myosin-I, and verprolin with Arp2/3 complex of motile cells. Front. Biosci. 2, d260–d270. London, Gower St, London WC1E 6BT, UK. during actin patch assembly in fission yeast. 20. Cramer, L.P. (1999). Organization and polarity E-mail: [email protected] J. Cell Biol. 170, 637–648. of actin filament networks in cells: implications 18. Sun, Y., Martin, A.C., and Drubin, D.G. (2006). for the mechanism of myosin-based cell Endocytic internalization in budding yeast motility. Biochem. Soc. Symp. 65, 173–205. DOI: 10.1016/j.cub.2008.09.048

Action Recognition: Is It a Motor familiar gestures that do not involve objects (intransitive gestures, such Process? as waving goodbye). Several studies [10–12] have reported correlations across groups of patients between A new study has found that brain-damaged patients impaired in the production their ability to produce actions and their of an action also find it difficult to recognize the sound of the same action, ability to recognize and/or imitate providing new insights into the complex relationship between action visually presented actions (performed production and action recognition. with the hand/arm). These data are consistent with the motor theory of Bradford Z. Mahon literature using a range of methods — action recognition. But a number of such as functional magnetic resonance studies have shown that patients with How do we recognize the actions of imaging and transcranial magnetic apraxic impairments may be relatively other individuals? Motor theories of stimulation — has described the unimpaired for recognizing the same perception argue that motor processes putative human homologues of the actions that they cannot produce play an active and necessary role in macaque mirror neuron system (for ([11–17]; see also Table S2 in [1]). This the recognition of familiar actions. The review, see [3]; and see Dinstein et al. means that successful action basic claim of this class of theories is [8] for healthy skepticism about the recognition does not require the normal that perceived actions are mapped empirical basis of the mirror neuron functioning of the action production onto the motor routines that would be system). system, and is at variance with the required in order to produce those The motor theory of action central prediction made by the motor same actions. Through the activation recognition faces two major theory of action recognition [18,19]. of those motor routines, the observer challenges. First, it is difficult to Pazzaglia et al. [1] now report new is then able to recognize, and determine whether the motor system is data in the auditory domain that meaningfully interpret, the observed activated during perception because address the two major challenges action. A central prediction of motor motor processes are necessary for faced by the motor theory of action theories of action recognition is that perception, supportive but not recognition. The authors defined when motor processes are necessary, or merely connected to, different groups of patients on the compromised, recognition processes but not functionally relevant for, basis of their ability to imitate the should be similarly affected. In this perception. Experiments that actions of another individual. One issue, Pazzaglia et al. [1] report new demonstrate that the motor system is group of patients, with buccofacial neuropsychological evidence automatically engaged during action apraxia, were differentially impaired at suggesting a close link between perception do not distinguish among imitating actions involving the mouth; impairments for producing actions these interpretations. This is because another group, with limb apraxia, were and impairments for recognizing the a theory is lacking about the dynamics differentially impaired at imitating sounds of actions. of how information is exchanged actions performed by the hand/limb [1]. The motor theory of perception was among (potentially distinct) perceptual All of the patients were then tested on initially developed in the domain of and motor processes [9]. their ability to match sounds to speech perception by Liberman et al. The second challenge faced by the pictures. The sounds were the [2]. The theory has since been motor theory of action recognition canonical sounds that are produced expanded and applied to visual and comes from neuropsychological either by mouth actions (for example, auditory action recognition [3], object studies of patients with apraxia. slurping soup), limb actions (for recognition ([4], but see [5]), and even Apraxia is an impairment for action example, using scissors), or mental state attribution ([6], but see [7]). production that cannot be explained non-human related environmental These extensions of the motor theory by low-level muscle or motor sounds (for example, airplane flying). of perception were spurred by disturbances, nor by an inability to The authors found that patients with Rizzolatti and colleagues’ observation comprehend the task (as, for example, (selective) buccofacial apraxia were that some neurons in frontal and because of problems with perception differentially impaired for the parietal motor structures of the or language understanding). For sound-picture matching task for macaque monkey brain discharge instance, apraxic patients may be mouth-related actions. In contrast, during both the execution and impaired at demonstrating the use of patients with (selective) limb apraxia observation of actions — these are the objects (transitive actions, such as were differentially impaired for so-called ‘mirror’ neurons. A growing using a hammer), and/or performing sound-picture matching for