Dynein and Kinesin

Abstract

During the life cycle of a eukaryotic cell, chromosomes and other cellular materials must be distributed to daughter cells, proteins must be synthesised and delivered to their site of utilisation and cellular organelles must be delivered to, and retrieved from, appropriate places within the cell. In some cell types, such as neurons, essential cellular materials must be delivered across long distances from the cell body to distal axon terminals or dendrites. Because diffusion is incapable of accomplishing these tasks, eukaryotes have developed an active transport mechanism that relies on superfamilies of kinesin, dynein and myosin motor proteins that walk along microtubule or microfilament tracks. This article discusses how the microtubule‐based motors of the kinesin and dynein superfamilies mediate intracellular transport and cilia/flagella motility within eukaryotic cells.

Key Concepts

  • Microtubules have an intrinsic polarity that microtubule‐based motor proteins recognise to generate adenosine triphosphate (ATP)‐dependent unidirectional movement.
  • Both the kinesin and dynein catalytic polypeptides contain a stand‐alone motor domain, which is the actual microtubule‐dependent ATPase force‐generating unit of these motors.
  • Axonemal dyneins, which comprise the outer and inner dynein arms, power cilia and flagella beating by producing sliding movements between adjacent outer‐doublet microtubules.
  • Cytoplasmic dyneins are primarily transport motors driving retrograde transport through a minus‐end‐directed ATP‐dependent mechanism.
  • In neurons, dynein complexes with different intermediate chain isoforms have distinct roles, including cargo binding and transport, and phosphorylation of the intermediate chain may also specify binding to specific cargo.
  • Differences in the stalk and tail domains and various associated proteins (light chains) distinguish the multiple classes of kinesin superfamily members.
  • A key functional distinction between dyneins and kinesins is that, while kinesin family members can generate movement in the plus‐ or minus‐end direction, dynein motors generate only minus‐end‐directed movement.
  • To fill the numerous intracellular roles for plus‐end‐directed motility, eukaryotic cells have evolved a large array of kinesin superfamily members.
  • Microtubule‐based motors must be regulated on an individual and collective scale to facilitate the correct temporal and spatial intracellular placement of eukaryotic organelles.
  • Cytoplasmic dynein and its dynactin complex drive retrograde, minus‐end‐directed movement in neurons, whereas kinesins typically move towards the anterograde direction.

Keywords: kinesin; dynein; cilia and flagella motility; organelle transport; microtubule‐based motors; axonal transport

Figure 1. (a) Microtubule‐based motors of the dynein superfamily and some members of the kinesin superfamily move towards the minus end of microtubules; most members of the kinesin superfamily move towards the plus end of microtubules. (b) Dynein motors exist as either two‐ or three‐headed structures. Dynein complexes have three structural domains: the stalk (red), the globular heads (blue) and the stem (green). (c) Kinesin‐I is a heterotetramer consisting of two identical heavy chains (red, green and blue) and two identical light chains (grey). The kinesin heavy chain has three functional domains: the motor domain (red), the α‐helical stalk domain (green) and the globular tail domain (blue). (d) Kinesin superfamily members all share a conserved kinesin motor domain (coloured circles) but have many different morphological structures.
Figure 2. (a) Diagram of the domain organisation of a single dynein heavy chain and (b) a schematic model of dynein movement in the post‐ and pre‐power‐stroke conformations. Movement and stroke conformation are depicted here from + end (right) to − end (left). (c) Schematic drawing of a cross‐section of flagellar axonemes. The nine outer‐doublet microtubules (green open circles), composed of an A and B tubule, surround the two central microtubules (red circles). Radial spokes (blue) extend out from the central pair complex (red) towards the outer‐doublet complex (green). The outer‐doublet complex contains two classes of dynein motors attached at their base to the A tubule. The inner arms are two‐headed dynein motor complexes, while the outer arms are three‐headed dynein motor complexes. For high‐resolution analysis of the structural mechanism of the dynein power stroke, see Lin et al., .
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Steele, John W, and Goldstein, Lawrence SB(Oct 2015) Dynein and Kinesin. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0000677.pub2]