Kinesin in nerve axons
Axonal transport is an important process, and some recent reviews are listed
below. There are multiple axonal transport systems, which operate with specific cargoes at different speeds, and in different directions. Although kinesin (being smaller) has received the greater attention, dynein and the regulatory complex dynactin also have a role in cytoplasmic transport.
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.
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.
Altar, CA & Distefano, PS (1998) Neurotrophin trafficking by anterograde transport. Trends in Neurosciences 21(10), 433-437. [Nerve growth factors are synthesised in the cell body, and transported anterogradely by central and peripheral neurons. No electronic copies are available.]
Block, SM (1998) Kinesin: What gives? Cell 93(1), 5-8. [No electronic copies are available.]
Cowan WM (1998) The emergence of modern neuroanatomy and developmental neurobiology. Neuron 20(3), 413-426. [No electronic copies are available.]
Endow, SA & Waligora, KW (1998) Determinants of kinesin motor polarity. Science 281(5380), 1200-1202. [No electronic copies are available.]
Gindhart, JG et al (1998) Kinesin light chains are essential for axonal transport in Drosophila. J. Cell Biol. 141(2), 443-454. [Click HERE for HTML format, or HERE for the PDF version.]
Hirokawa, N et al (1998) Kinesin and dynein superfamily proteins in organelle transport and cell division. Current Opinion in Cell Biology 10(1), 60-73. [Excellent review. No electronic copies are available.]
Kozielski, F et al (1997) The crystal structure of dimeric kinesin and implications for microtubule-dependent motility. Cell 91(7), 985-994. [No electronic copies are available.]
Kristensson, K (1996) Sorting signals and targeting of infectious agents through axons: An annotation to the 100 years' birth of the name "axon". Brain Research Bulletin 41(6), 327-333. [This article is mainly about axonal transport. No electronic copies are available.]
Mandelkow, E & Johnson, KA (1998) The structural and mechanochemical cycle of kinesin. TIBS 23(11), 429-433. [No electronic copies are available.]
Okada, Y & Hirokawa, N (1999) A processive single-headed motor: Kinesin superfamily protein KIF1A. Science 283(5405), 1152-1157. [No electronic copies are available.]
Pierce, DW & Vale, RD (1998) Assaying processive movement of kinesin by fluorescence microscopy. Methods In Enzymology 298, 154-171. [No electronic copies are available.]
Sablin, EP et al (1998) Direction determination in the minus-end-directed kinesin motor ncd. Nature 395(6704), 813-816. [Write down the volume and page numbers for future reference. Click HERE for access instructions. Click HERE to gain access via the Leeds University network.]
Sack, S et al (1999) Motor proteins of the kinesin family - Structures, variations, and nucleotide binding sites. Europ. J. Biochem. 262(1), 1-11. [You will probably need to log in to read this using the usual BIDS password, but an automated system is on the way. Write down the volume and page numbers for future reference. Click HERE for the journal home page, from which you can navigate to the full text PDF version.]
Sheetz, MP et al (1998) Mechanisms of trafficking in axons and dendrites: Implications for development and neurodegeneration. Progress in Neurobiology 55(6), 577-594. [No electronic copies are available.]
Song, HB & Endow, SA (1998) Decoupling of nucleotide- and microtubule-binding sites in a kinesin mutant. Nature 396(6711), 587-590. [Write down the volume and page numbers for future reference. Click HERE for access instructions. Click HERE to gain access via the Leeds University network.]
Tanaka, Y et al (1998) Targeted disruption of mouse conventional kinesin heavy chain, kif5B, results in abnormal perinuclear clustering of mitochondria. Cell 93(7), 1147-1158. [No electronic copies are available.]
Vale, RD & Fletterick, RJ The design plan of kinesin motors. (1997) Annual Review of Cell and Developmental Biology 13, 745-777. [Excellent review. Click HERE for HTML format, or HERE for the PDF version.]
Visscher, K et al (1999) Single kinesin molecules studied with a molecular force clamp. Nature 400(6740), 184-189. [Write down the volume and page numbers for future reference. Click HERE for access instructions. Click HERE to gain access via the Leeds University network.]
The molecular mechanism of the kinesin motor has been extensively studied
using laser-based “optical tweezers” to manipulate microscopic beads linked to individual protein molecules. In this way it has been possible to discover the step length, step frequency and the work done per ATP hydrolysed. See for example:
Block, SM (1995) Trends in Cell Biology 5, 169-175.
Correia, JJ et al (1995) Biochemistry 34, 4898-4907.
Gelles, J et al (1995) Biophysical Journal 68, 276s-282s.
Howard, J (1995) Biophysical Journal 68, 254s-255s.
Howard, J (1996) Ann. Rev. Physiol. 58, 703-729.
Kuo, SC et al (1995) Biophysical Journal 68, 74s.
Meyhöfer, E & Howard, J (1995) Proc. Nat. Acad. Sci. USA 92, 574-578.
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If you have comments, queries or suggestions, email me at J.A.Illingworth@leeds.ac.uk