Mitotic Spindle Assembly: The Role of Motor Proteins

Abstract

The mitotic spindle, a microtubule‐based structure, is required for chromosome segregation during cell division. Motor proteins are molecular machines that utilise the energy of adenosine triphosphate (ATP) hydrolysis to move along microtubules. During cell division, motor proteins are required for spindle formation, chromosome alignment and segregation. Thus, mitotic motor proteins are required for the cell to avoid aneuploidy, a hallmark of cancer.

Key Concepts:

  • Molecular motors, including dynein/dynactin and several families of kinesin, are required for mitosis.

  • Kinesins contribute to establishing spindle bipolarity, positioning chromosomes between spindle poles and focusing spindle poles.

  • Dynein contributes to the metaphase checkpoint, spindle positioning, regulating spindle length and pole focusing.

  • To establish and maintain a mitotic spindle, motor proteins achieve a balance of forces on microtubules.

Keywords: Mitosis; kinesin; dynein; spindle; spindle assembly; motor protein; microtubule; ATP hydrolysis

Figure 1.

Schematic representation of a mammalian metaphase spindle. Three categories of microtubules (grey; interpolar, astral and kinetochore) are shown assembled into a bipolar structure. Pericentriolar microtubule‐nucleating material (light green) and centrioles (dark green) make up the centrosome. An exemplary chromosome (blue) is shown with a kinetochore fibre linking the kinetochores (purple) of the sister chromatids (blue) to the spindle poles (green).

Figure 2.

Phases of mitosis. Mammalian pig kidney epithelial cells (LLC‐Pk1) were fixed and stained with antibodies targeting tubulin (green) and Hec1, a kinetochore marker (red, top row) or propidium iodide to stain chromosomes (red, bottom row). Each cell shows a different phase of mitosis, as indicated above the micrograph. Fluorescence micrographs were imaged using a spinning disc confocal microscope, and are shown as deconvolved maximum X–Y projections (top row) or maximum X–Y projections (bottom row).

Figure 3.

ATPase cycle of kinesin. (a) Kinesin encounters the microtubule with the leading head (light grey) in the ADP nucleotide state. (b) The leading head exchanges ADP for ATP and the lagging head (dark grey) swings forward (motion depicted by arrow). (c) Both heads are bound to the microtubule. (d) The lagging head (light grey) hydrolyses ATP to ADP and inorganic phosphate, releasing the head from the microtubule and the leading head (dark grey) then binds ATP, starting the cycle again (b–d).

Figure 4.

Contribution of kinesins during spindle assembly. Mitotic kinesins: Kinesin‐5 (purple) binds and slides apart antiparallel microtubules. Kinesin‐12 (orange) binds one microtubule with its motor heads, while interacting with a linker protein bound to a second microtubule (light grey). Kinesin‐14 (light blue) binds one microtubule with its motor domains, while passively binding a second microtubule with its tail domains. Kinesin‐4 and Kinesin‐10 bind to chromosome arms (blue) with their tails and to microtubules with their motor domains. Kinesin‐13 is at the microtubule ends at the spindle pole (green) and kinetochores (purple), where it depolymerises the microtubule into tubulin dimers (short dark grey objects). Kinesin‐7 and Kinesin‐8 bind the kinetochore with their tails and to the microtubule with their motor domains. Dynein/dynactin: (Left) Dynein/dynactin (dark and light purple, respectively) binds two microtubules. (Middle) Dynein/dynactin removes checkpoint proteins from kinetochores. (Right) Dynein/dynactin anchored at the cell cortex moves astral microtubules.

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References

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Further Reading

Alberts B, Johnson A, Lewis J et al. (2007) Molecular Biology of the Cell, 5th edn. NewYork: Garland Publishing.

Lewin B, Cassimeris L, Lingappa VR and Plopper G (2011) Cells, 2nd edn. Sudbury, MA: Jones and Bartlett Publishers.

Wittman T, Hyman A and Desai A (2001) The spindle: a dynamic assembly of microtubules and motors. Nature Cell Biology 3: E28–E34.

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How to Cite close
Titus, Janel, and Wadsworth, Patricia(Jul 2012) Mitotic Spindle Assembly: The Role of Motor Proteins. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0022519]