School of Biochemistry 
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BIOC3390: Linear Motors

Dr JA Illingworth

This site deals with the linear motors myosin, kinesin and dynein. There are many other kinds of molecular motors, including chaperones, rotary motors like the F1 ATPase and bacterial flagella, nucleic acid motors such as helicases and topoisomerases, and the motors responsible for peptide and nucleic acid translocation during ribosomal protein synthesis.

Numerous references are listed below, most of them with electronic full-text access from the Leeds University Campus. You only have time to read a few of these, and students should visit a representative selection on topics that they find interesting. If we set examination questions in this area we will try to give you plenty of choice.



These are multiple copy text-books that are available from the University Libraries. Click the links to locate the current holdings.

See also Higgins & Banting Essays in Biochem. 35 - Molecular Motors Portland Press; 2000 [Hartley Library only]

There is a complete issue of BBA Molecular Cell Research (volume 1496) published in March 2000 that is full of reviews on molecular motors: various types of myosin, dynein and kinesin. It is available on line. If you only read one journal for this topic, this is the one to go for!

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Our knowledge of these motor proteins is inversely proportional to their molecular weight. In some cases, isolated protein domains have increased our understanding. The smallest motor is kinesin where the mechanics are fairly well understood, followed by myosin, and finally dynein, which is huge and something of a mystery.

Kinesin and cytoplasmic dynein are processive motors. There are two head groups, which are thought to function alternately. One head group binds to the tubulin while the other advances to the next binding site. (There are some reports of single-headed processive motors, which are difficult to reconcile with this account!) In any event, the motor remains firmly attached to the microtubule for considerable distances, and this enables a single motor to transport large organelles without losing its grip. Myosin in contrast normally binds only briefly to actin during its catalytic cycle, but this brief contact is sufficient because there are about 250 myosin molecules in every thick filament. The structure of the sarcomeres ensures that the actin and myosin do not drift apart.

For dynein in cilia we are looking at a bending movement. All the 9 + 2 microtubules in each axoneme are connected at the basal body, and the dynein pulls one microtubule in the cilium against its neighbour, causing the shaft to bend. The coordinated whiplash movements of the cilia expel the mucus from the lungs. Cilia are very complex structures with over 100 protein components, and are not well understood.

Movement of materials through the cytosol is an important constraint on the performance of living cells. Motor neurones need to drag many of the major cellular components from their site of synthesis in the cell body near the nucleus down the axon to their point of use at the motor endplate, which in humans may be about 1 metre distant. If you think that is difficult, imagine the task faced by the corresponding cells in a giraffe or a whale. Not only do cells need to export the new material, but they also need to retrieve used or damaged components. Do not forget the need to get the microtubule 'railway' itself into position and perform routine maintenance for seventy years when individual items fail.

The problem is obvious in long thin cells like motor neurones, but diffusion is also a constraint in ordinary cuboidal epithelial cells. Each individual cilium has its own internal transport system, because otherwise it would be impossible to get material to the far end fast enough for it to perform its function. There has been sustained selection pressure in this area over the last 2,000,000,000 years: sperm tails are specialised cilia, and are used for a competition where there are no second prizes.

Brown (1999) Cooperation between microtubule- and actin-based motor proteins Annu. Rev. Cell Dev. Biol. 15, 63-80.

Goldstein & Yang (2000) Microtubule-Based Transport Systems in Neurons: The Roles of Kinesins and Dyneins Annu. Rev. Neurosci. 23, 39-71.

Muresan (2000) One axon, many kinesins: What's the logic? J. Neurocytology 29(11-12), 799-818.

Nogales (2000) Structural Insights Into Microtubule Function Annu. Rev. Biochem. 69, 277-302 (There is a coding error on this website: use the pdf version.)

Schafer (1999) Actin-related proteins Annu. Rev. Cell Dev. Biol. 15, 341-363.

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Single molecule techniques using optical tweezers have been used to study the force generation mechanisms in several molecular motors. It is possible to measure both the maximum force generated and the distance moved per catalytic cycle. These measurements are made at the limits of instrumental resolution, and there remains some uncertainty about the precise values.

Ashkin, A (1997) Optical trapping and manipulation of neutral particles using lasers Proc. Nat. Acad. Sci. USA 94, 4853-4860.

Fisher, ME & Kolomeisky, AB (1999) The force exerted by a molecular motor. Proc. Natl. Acad. Sci. USA 96(12), 6597-6602.

Knight et al (2001) Analysis of single-molecule mechanical recordings: application to acto-myosin interactions Progress In Biophysics & Molecular Biology 77(1), 45-72.

Mehta, AD, Pullen, KA & Spudich, JA (1998) Single molecule biochemistry using optical tweezers FEBS Letters 430, 23-27.

Mehta, AD et al (1999) Single-molecule biomechanics with optical methods. Science 283(5408), 1689-1695.

Visscher, K & Block, SM (1998) Versatile optical traps with feedback control. Methods In Enzymology 298, 460-489. [This is a technical account of the experimental techniques. No electronic copies are available.]

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Try to recall some basic physics: work done = force * distance moved. A force of 1 Newton moving 1 metre requires 1 Joule of energy. So a force of 1 piconewton moving 1 nanometre requires 10E-21 Joules. The free energy of hydrolysis of ATP under typical intracellular conditions is about 50 kJ / mole [6.022 x 10E23 molecules], so each individual molecule of ATP could supply about 8 x 10E-20 Joules. What would be the maximum force * distance for a molecular motor for each ATP split, assuming 100% conversion efficiency from chemical energy into mechanical energy?

Try to put your estimates in context. A typical 70 Kg human being breathes ~10,000 litres of air each day. The exhaled gases contain ~5% CO2 i.e. ~22 moles of carbon in total. If (for example) this energy were derived equally from fats and carbohydrate, we would be looking at a total input of ~11 MJ per day, phosphorylating over 100 moles of ATP (almost 60 Kg!) with a net conversion efficiency approaching 50%. These are average figures, including tissues which are metabolically inert.

It turns out that the maximum efficiency of the linear motors is also about 50%, so the conversion of food energy into muscular work is no better than 25% overall (not bad really!) and at least 75% is lost as heat. In practice, most of our molecular motors are doing internal work moving things around inside cells as described below, so very little of the energy derived from our food is actually used to perform mechanical work on our external environment.

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Cell Division (overview)

contractile ring contractile ring kinetochore kinetochore kinetochore kinetochore pole spindle pole dynein dynein dynein dynein dynein dynein dynein dynein chromosomes chromosomes


Point [don't click] with the mouse at the features on this diagram for an explanation.

Prophase: the spindle poles separate, the sister chromatids condense and the nuclear membrane disperses.

Metaphase: the sister chromatids are aligned at the middle of the cell.

Anaphase: the cell elongates, the daughter chromosomes separate and are dragged towards the spindle poles.

Telophase: the nuclear membranes reform and cytoplasmic division is completed.

  • see Lodish et al chapter 19
    pages 823 - 836

Recent papers and reviews:

Brunet & Vernos (2001) Chromosome motors on the move - From motion to spindle checkpoint activity EMBO Reports 2(8), 669-673.

Doxsey (2001) Re-evaluating centrosome function Nature Reviews Molecular Cell Biology 2(9), 688-698.

Endow, SA (1999) Microtubule motors in spindle and chromosome motility. Europ. J. Biochem. 262(1), 12-18.

Faulkner et al (2000) A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function Nature Cell Biology 2(11), 784 - 791.

Glotzer (2001) Animal Cell Cytokinesis Annu. Rev. Cell Dev. Biol. 17, 351-386.

Heald (2000) Cell 102, 399 - 402 provides an excellent minireview of two full papers on the chromokinesin Xkid (by Antonio et al and Funabiki et al) in the same issue of this journal. The Xkid motor protein aligns the sister chromatids in the metaphase plate, and must be degraded before anaphase can commence.

Scholey et al (2001) Mitosis, microtubules, and the matrix J. Cell Biology 154(2), 261-266.

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Duke (1999) Molecular model of muscle contraction. Proc. Natl. Acad. Sci. USA 96(6), 2770-2775.

Geeves & Holmes (1999) Structural mechanism of muscle contraction Annu. Rev. Biochem. 68, 687-728.

Ruff et al. (2001) Single-molecule tracking of myosins with genetically engineered amplifier domains Nature Structural Biology 8(3), 226-229.

Spudich (2001) The myosin swinging cross-bridge model Nature Reviews in Molecular Cell Biology 2(5), 387-392.

The motor domain is a relatively constant feature of the numerous myosin variants, but the remainder of these molecules shows enormous variation, in keeping with their differing physiological functions. The following figure derives from the Cambridge MRC muscle website, which specialises in clustal analysis of the myosin genes.

Non-muscle myosins are required for cytokinesis at the end of cell division, when a contractile ring near the plasmalemma divides the cytoplasm of the daughter cells. They are involved in cytoplasmic streaming movements in many tissues, and especially in actively motile cells such as fibroblasts and macrophages. Special myosin variants are required for sensory processes involved in hearing and vision.

Bridgman & Elkin (2000) Axonal myosins J. Neurocytol. 29, 831-841 Back to the table of contents


The unexpected roles of myosin in hearing and vision have attracted considerable medical interest. It seems likely that myosins are involved in the correct assembly of melanosomes within the pigmented layer of the retina, and also in the correct differentiation of hair cells within the inner ear. These cells display actin-based stereocilia which transduce sound waves and the movement of fluid in the semicircular canals into nerve impulses. In addition to the roles of myosin isoforms in hair cell differentiation, myosin has a further function in the adaptation of the hearing transducer to cope with loud and faint noises. The adaptation motor is thought to be myosin 1 beta, which slides an actin-based "needle valve" to almost block an ion channel in the hair cell membrane. Sound vibrations displace the membrane, allowing ions to enter the cell, and this is thought to initiate the signaling process.

The central point is that all hair cells are motile, negative feedback systems, actively changing their shape in response to membrane potential, as well as changing their membrane potential in response to deformation. There is specialisation, in that the inner hair cells are mostly sensory, whereas the more numerous outer hair cells have an obvious motor function. The main function of the cochlear amplifier is to select particular frequencies in the face of much louder background noises. There is also an overall volume control through the reflex contraction of the tensor tympani and stapedius muscles in the middle ear when the subject is exposed to loud noises, thereby reducing the movement of the auditory ossicles.

Usher syndromes type IA (dynein) and type 1B (myosin 7A) are autosomal recessive disorders characterised by profound congenital deafness, vestibular areflexia, and progressive retinitis pigmentosa. Nonsyndromic deafness results from mutations in myosin 15, myosin 7 and possibly in the myosin 9 and MYO1D genes. Myosin 6 is also a strong candidate gene, which encodes the only known myosin motor directed toward the minus end of actin filaments. There is a recent review by Willems (2000) Genetic Causes of Hearing Loss New England J. Med. 342(15) 1101 - 1109. [Students must contact the Leeds University Library help desk in person for the password for this site.] Mouse "dilute" mutations (myosin 5A) are associated with neurological deficits, although the analogous Griscelli syndrome in humans apparently has no neural component.

Ashmore & Mammano (2001) Can you still see the cochlea for the molecules? Current Opinion In Neurobiology 11(4), 449-454.

Eatock (2000) Adaptation in Hair Cells Annu. Rev. Neurosci. 23, 285-314.

Gillespie & Walker (2001) Molecular basis of mechanosensory transduction Nature 413(6852), 194-202.

Holt & Corey (2000) Two mechanisms for transducer adaptation in vertebrate hair cells Proc. Natl. Acad. Sci. USA 97(22), 11730-11735.

Hudspeth et al (2000) Putting ion channels to work: Mechanoelectrical transduction, adaptation, and amplification by hair cells Proc. Natl. Acad. Sci. USA 97(22), 11765-11772.

Martin et al (2000) Negative hair-bundle stiffness betrays a mechanism for mechanical amplification by the hair cell Proc. Natl. Acad. Sci. USA 97(22), 12026-12031.

Muller & Littlewood-Evans (2001) Mechanisms that regulate mechanosensory hair cell differentiation Trends In Cell Biology 11(8), 334-342.

Petit (2001) Usher syndrome: from genetics to pathogenesis Annu. Rev. Genom. Human. Genet. 2, 271-297.

De la Cruz et al. (2001) Kinetic mechanism and regulation of myosin VI J. Biol. Chem. 276(34), 32373-32381.

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Cell migration

Cells migrate by extending actin-stiffened "ruffles" (lamellipodia) at the front which form new focal adhesions to the substrate, then dragging the cell body forwards, and finally letting go of the old focal adhesions at the rear. Myosin I provides the motive power at the leading edge of the cell, and myosin II at the rear.

Geiger & Bershadsky (2001) Assembly and mechanosensory function of focal contacts Current Opinion In Cell Biology 13(5), 584-592.

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Vesicular Motors

Myosin I and Myosin V are both involved in vesicular trafficking, particularly that involving the Golgi apparatus and the cell membrane. Trafficking is normally a two-way activity (you have to collect the "empties") but it is not clear at present which myosin variants are responsible for which stages of the process.

Karcher et al. (2001) Cell cycle regulation of myosin-V by calcium/calmodulin-dependent protein kinase II Science 293(5533), 1317-1320.

Mehta (2001) Myosin learns to walk J. Cell Science 114(11), 1981-1998.

Veigel, C et al (1999) The motor protein myosin-I produces its working stroke in two steps. Nature 398(6727), 530-533.

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Circumferential belt

There is a circular actomyosin contractile bundle underlying the adherens junction between adjacent epithelial cells. This is important for closing any gaps in the sheet of cells and healing wounds.

Mandato & Bement (2001) Contraction and polymerization cooperate to assemble and close actomyosin rings around Xenopus oocyte wounds J. Cell Biol. 154(4), 785-797.

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Cell division motors (cytokinesis)

Myosin II powers the contractile band that forms around the equator of dividing cells after nuclear division is complete, and squeezes the cytoplasm into two daughter cells.

Komatsu et al. (2000) Effects of the regulatory light chain phosphorylation of myosin II on mitosis and cytokinesis of mammalian cells J. Biol. Chem. 275(44), 34512-34520.

Poperechnaya et al.(2000) Localization and activity of myosin light chain kinase isoforms during the cell cycle J. Cell Biol. 151(3), 697-707.

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Kinesin and kinesin related proteins

This is the X-ray structure of rat kinesin, reported by Kozielski et al in 1997. [Brookhaven code 3KIN.] Note the two head groups and the long helical tail, by which the cargo is attached. Switch to ribbon view and colour in the four protein strands. Click HERE for a brief reminder of the main CHIME commands, or HERE for a full tutorial. Rotate the molecule and experiment with different views to study the mechanism.

Most kinesins and kinesin related proteins are + end directed motors, but - end directed variants are known in the cell division apparatus.

For much useful background information, and some nice movies of molecular motors moving things, visit the kinesin home page hosted by the Fred Hutchinson Cancer Research Center in Washington. It is worth taking some time to explore this site, which includes an illustrated account of organelle jams in the Khc mutants in Drosophila.

Goldstein (2001) Kinesin molecular motors: Transport pathways, receptors, and human disease Proc. Natl. Acad. Sci. USA 98(13), 6999-7003.

Goldstein & Philp (1999) Emerging Principles of Kinesin Motor Utilization Annu. Rev. Cell Dev. Biol. 15, 141-183.

Kikkawa et al. (2001) Switch-based mechanism of kinesin motors Nature 411(6836), 439-445.

Schnitzer et al (2000) Force production by single kinesin motors Nature Cell Biology 2(10), 718 - 723.


The photoreceptors on the rod and cone cells are greatly modified cilia. In addition to the contractile protein dynein, which is responsible for bending, normal cilia also contain a kinesin-based transport system that moves internal components to the far end of each cilium. This mechanism is exploited in the photoreceptors for opsin transport, and mutations in this molecular motor lead to blindness.

Retinitis pigmentosa is a common cause of blindness. It is often caused by rhodopsin mutations, but may also result from mitochondrial defects and a failure of kinesin II to transport opsin into the photoreceptors. KIF1A gene knockout produces motor and sensory defects in mice through a failure in synaptic vesicle transport. No human equivalent has yet been identified. There is an excellent review by Fernald (2000) Evolution of eyes Current Opinion in Neurobiology 10(4) 444-450 which distinguishes the invertebrate photoreceptors based on microvilli from the vertebrate type which evolved from cilia.

Recent papers:

Marszalek et al (2000) Genetic evidence for selective transport of opsin and arrestin by kinesin-II in mammalian photoreceptors CELL 102,(2) 175-187. [no electronic copies]

There is a review on Rhodopsin trafficking and its role in retinal dystrophies by Sung & Tai (2000) International Review Of Cytology 195, 215-267 in the Health Sciences Library, but no electronic copies are available.

Forward axonal transport

Recent papers:

Galbraith & Gallant (2000) Axonal transport of tubulin and actin J. Neurocytol. 29, 889-911.

Kaether et al (2000) Axonal Membrane Proteins Are Transported in Distinct Carriers: A Two-Color Video Microscopy Study in Cultured Hippocampal Neurons Molecular Biology of the Cell 11(4), 1213 - 1224.

Roy et al (2000) Neurofilaments Are Transported Rapidly But Intermittently in Axons: Implications for Slow Axonal Transport J. Neurosci. 20(18), 6849 - 6861.

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Cell division motors (spindle microtubules)

deCastro et al (2000) Working strokes by single molecules of the kinesin-related microtubule motor ncd Nature Cell Biology 2(10), 724 - 729.

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Dynein and cytoplasmic dynein

Dyneins are usually minus end-directed motors, that pull on microtubules. There are two kinds of dynein: the protein found in cilia differs slightly from the cytosolic version responsible for pulling on the astral microtubules and reverse axonal transport. A rather complex multi-subunit protein called dynactin is required to attach the dynein molecules to their cytosolic cargoes.

King (2000) AAA domains and organization of the dynein motor unit J. Cell Science 113(14), 2521-2526.

Vaughan et al (2001) Cytoplasmic dynein intermediate chain phosphorylation regulates binding to dynactin J. Biol. Chem. 276(28), 26171-26179.

Cilia beating

Vitually all eukaryotic cilia and flagella have the same basic organisation, based on the 9+2 arrangement of microtubules illustrated in the diagram. The two inner microtubules are singlet structures, but the outer ring consists of 9 doublet microtubules, each bearing hundreds of dynein molecules distributed along their length.

The individual doublet microtubules are cross-linked by nexin and connected to the central structure by radial spokes. Consequently, when the dynein molecules in one doublet exert a force on the neighbouring doublet, the whole structure bends instead of the microtubules sliding against each other. This also requires that the activity of individual dynein molecules is regulated in some way.

Dynein molecules towards the outside of the cilium have three functional head groups, but those on the inside have only two.

In addition to the bending motility of the axonemes, there are separate anterograde and retrograde transport systems inside each cilium / flagellum to assemble and replace the protein components, and a third system responsible for surface motility on the plasmalemma surrounding the organelle. One of the dynein light chains is essential for the retrograde transport system.

For an introduction to pulmonary function, consult one of the physiology texts in the medical library, or visit the Cornell Medical Center website. [First click the courseware icon, then go to pathology notes, then go to respiratory. Click on the coloured icons to inspect individual histology slides.] Tracheal cilia beat about 20 times per second, and the activities of adjacent cells are synchronised by travelling calcium waves. Shovelling mucus is hard work, but it is essential for normal life: Kartagener syndrome and immotile cilia syndrome are autosomal recessive disorders characterised by bronchiectasis, sinusitis, dextrocardia, and infertility. Patients with Kartagener syndrome have defective dynein arms and suffer from chronic respiratory disease, immotile sperm and left/right inversion of the viscera. Cilia are extremely complex structures, and contain many other components that might go wrong, in addition to the molecular motors.

Iomini et al (2001) Protein particles in Chlamydomonas flagella undergo a transport cycle consisting of four phases J. Cell Biol. 153(1), 13-24.

Sakakibara, H et al (1999) Inner-arm dynein c of Chlamydomonas flagella is a single-headed processive motor. Nature 400(6744), 586-590.

Yang et al (2001) Localization of calmodulin and dynein light chain LC8 in flagellar radial spokes J. Cell Biol. 153(6), 1315-1325.

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Reverse axonal transport

Recent papers:

Bearer et al (2000) Retrograde axonal transport of herpes simplex virus: Evidence for a single mechanism and a role for tegument Proc. Natl. Acad. Sci. USA 97(14), 8146-8150.

Susalka & Pfister (2000) Cytoplasmic dynein subunit heterogeneity: implications for axonal transport J. Neurocytol. 29, 819-829.

Shea (2000) Microtubule motors, phosphorylation and axonal transport of neurofilaments J. Neurocytol. 29, 873-887.

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Cell division motors (astral microtubules)

O'Connell & Wang (2000) Mammalian Spindle Orientation and Position Respond to Changes in Cell Shape in a Dynein-dependent Fashion Mol. Biol. Cell 11, 1765-1774.

Dionne et al (2000) ch-TOGp is required for microtubule aster formation in a mammalian mitotic extract J. Biol. Chem. 275(16), 12346-12352.

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