Key Points
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Vertebrate myosin Va is structurally and kinetically designed to be able to move processively along actin filaments as a single molecule and is thus well suited to be a cargo transporter. The key features are the presence of two motor domains and kinetics with a high duty ratio.
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Not all class V myosins are structurally or kinetically similar to vertebrate myosin Va. Some do not have high duty ratios and are not two headed. These class V myosins must adopt other strategies to move cargo, such as having multiple motors bound to the cargo.
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Budding yeast and plants build actin cytoskeletons that are suitable for long range class V myosin-dependent cargo transport. Indeed, the yeast class V myosins Myo2 and Myo4 drive most, if not all, organelle transport in this organism.
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The organization of actin within the cortex of vertebrate cells is largely anisotropic, so the class V myosin-dependent transport of organelles in these cells, which in most cases will follow the long-range transport of the organelle on microtubules to the cell periphery, is likely to exhibit minimal directional persistence and be very local.
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Two recent and compelling examples of class V myosin-dependent organelle transport have been identified within the dendritic spines of neurons, one involving recycling endosomes, and the other involving the endoplasmic reticulum.
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The 'acid test' as to whether a class V myosin actually moves an organelle in vivo is to show that the organelle moves more slowly when the cell expresses a 'slower' version of the class V myosin.
Abstract
Cells use molecular motors, such as myosins, to move, position and segregate their organelles. Class V myosins possess biochemical and structural properties that should make them ideal actin-based cargo transporters. Indeed, studies show that class V myosins function as cargo transporters in yeast, moving a range of organelles, such as the vacuole, peroxisomes and secretory vesicles. There is also increasing evidence in vertebrate cells that class V myosins not only tether organelles to actin but also can serve as short-range, point-to-point organelle transporters, usually following long-range, microtubule-dependent organelle transport.
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Acknowledgements
We thank M. Peckham for drafting figure 1. For space reasons, we have not included many examples in which the evidence of class V myosin-dependant organelle transport, although suggestive, is not yet robust. We apologize to the authors of those studies for not citing their work.
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Glossary
- Power stroke
-
The distance that the lever arm of myosin moves in a single event.
- Brownian diffusion
-
The random, thermally driven motion of small objects in a fluid or gas.
- Optical trapping
-
A technique that uses focused laser light in a light microscope to capture and manipulate objects with dielectric constants different from water. Sophisticated traps can be used to measure the mechanical properties of single molecules of motor proteins, such as the class V myosins.
- Super-resolution light microscopy
-
Techniques that use Gaussian fits to the point spread function of light emitted from a single fluorophore to determine its position to within a few nanometres, which is significantly smaller than the diffraction limit.
- Total internal reflection fluorescence
-
(TIRF). TIRF microscopy provides improved signal to noise ratios at the interface between media with differing refractive indices (such as coverslip–water), where fluorescence is excited by an evanescent field of light created when the incident light is totally internally reflected. It is ideal for visualizing the movement of single motor proteins.
- High-speed atomic force microscope
-
(High-speed AFM). A modified AFM that can acquire images at a high rate from samples in aqueous solution, allowing the dynamic imaging of single molecules as they perform their tasks.
- Myosin II
-
Also called conventional muscle myosin. The first myosin type to be discovered and the most conspicuous of the myosin superfamily. It is responsible for skeletal muscle contraction in muscle cells.
- Duty ratio
-
The fractional time that a myosin spends in a state of high affinity for actin during an ATP hydrolysis cycle.
- Melanosome
-
The pigment-producing organelle found in pigment-producing cells, such as melanocytes.
- RAB switch
-
The sequential interaction of an effector protein with two different RAB GTPases.
- Exocyst
-
An eight-member protein complex that is required for vesicle docking and polarized exocytosis and is conserved from yeast to mammals.
- Myristoylation
-
A protein post-translational modification in which the 14-carbon saturated fatty acid myristic acid is covalently attached to an amino-terminal Gly residue.
- Palmitoylation
-
A protein post-translational modification in which the 16-carbon saturated fatty acid palmitic acid is covalently attached to a Cys residue.
- PEST site
-
A sequence within proteins that serves as a site for cleavage by the Ca2+- dependent protease calpain.
- Recycling endosome
-
A generic, centrally located membrane compartment that receives endocytosed membrane receptors and recycles them back to the plasma membrane.
- Long-term potentiation
-
(LTP). A form of synaptic plasticity that is thought to underlie memory formation, in which synapse use leads to long-term strengthening of the synapse.
- AMPA receptors
-
The major excitatory ionotropic Glu receptors found in neurons. Their name comes from their ability to be activated by the artificial Glu analogue AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid).
- Long-term depression
-
(LTD). A form of synaptic plasticity that is thought to underlie memory formation, in which synapse use leads to long-term weakening of the synapse.
- Anisotropic
-
A term referring to a complete lack of uniformity in orientation.
- Filopodia
-
Thin, dynamic, cellular extensions containing actin filaments aligned in parallel with their barbed ends pointing towards the tip. They are often found in growth cones and at the leading edge of migrating cells.
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Hammer, J., Sellers, J. Walking to work: roles for class V myosins as cargo transporters. Nat Rev Mol Cell Biol 13, 13–26 (2012). https://doi.org/10.1038/nrm3248
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DOI: https://doi.org/10.1038/nrm3248
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