Kinesin superfamily motor proteins and intracellular transport

Key Points

  • Forty-five genes that encode kinesin superfamily proteins (also known as KIFs) have been discovered in the mouse and human genomes.

  • KIFs are molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs, along the microtubule system.

  • The mechanisms by which different kinesins recognize, bind and unload specific cargo have been identified.

  • The spatiotemporal delivery of cargos by KIF-based transport can be regulated by phosphorylation, G proteins and Ca2+ levels.

  • It is now recognized that kinesins have unexpected roles in the regulation of physiological processes, such as higher brain function, tumour suppression and developmental patterning.

Abstract

Intracellular transport is fundamental for cellular function, survival and morphogenesis. Kinesin superfamily proteins (also known as KIFs) are important molecular motors that directionally transport various cargos, including membranous organelles, protein complexes and mRNAs. The mechanisms by which different kinesins recognize and bind to specific cargos, as well as how kinesins unload cargo and determine the direction of transport, have now been identified. Furthermore, recent molecular genetic experiments have uncovered important and unexpected roles for kinesins in the regulation of such physiological processes as higher brain function, tumour suppression and developmental patterning. These findings open exciting new areas of kinesin research.

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Figure 1: The structure and phylogeny of major mouse kinesins.
Figure 2: Intracellular transport by molecular motors in neurons, non-neuronal cells and cilia.
Figure 3: Kinesins, cargos and molecules involved in cargo recognition.
Figure 4: Regulation of kinesin–cargo binding by three different mechanisms.
Figure 5: The physiological relevance of kinesins in mice.

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Acknowledgements

The authors thank H. Fukuda, H. Sato and all other members of the Hirokawa laboratory for their technical assistance, support and discussion. This work was supported by a Grant-in-Aid for Specially Promoted Research to N. H. and a global COE programme to the University of Tokyo from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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DATABASES

OMIM

CFEOM1

Joubert syndrome

Kartagener syndrome

polycystic kidney

spinal and bulbar muscular atrophy

FURTHER INFORMATION

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Glossary

WD40 repeat

A protein motif that is composed of a 40 amino acid repeat that forms a blade of the characteristic β-propeller structure. Proteins that contain WD40 repeats participate in G protein-mediated signal transduction, transcriptional regulation, RNA processing and regulation of vesicle formation and trafficking.

Synaptophysin

A glycoprotein of 38 kDa that is localized to synaptic vesicle membranes.

Synaptotagmin

One of a group of Ca2+-binding proteins that are involved in the secretion of granules and vesicles, especially in the nervous system.

Haploinsufficiency

Occurs when a diploid organism has only a single functional copy of a gene that does not produce enough of a gene product to bring about a wild-type condition. This leads to an abnormal or diseased state.

Synaptobrevin

An integral synaptic vesicle protein of 18 kDa that is involved in the formation of the SNARE complex in exocytosis. Synaptobrevin is a major target of cleavage by tetanus toxin.

Armadillo repeat

A protein–protein interaction consensus stretch of 40 amino acids.

Tetratricopeptide motif

A loosely conserved domain of 30–40 amino acids that is involved in protein–protein interactions.

Voltage-gated potassium channel

A class of transmembrane channel that senses the electrical potential across the plasma membrane to open and admit K+ flow through the membrane.

Apical transport

A mode of organelle transport in polarized cells towards the apical surface of the cell.

Zonula adherens

A cell–cell adherens junction that forms a circumferential belt around the apical pole of epithelial cells.

Melanosome

An organelle that contains melanin, a common light-absorbing pigment.

Endomembrane

An intracellular lipid bilayer membrane that surrounds small spaces, for example to form vesicles and membrane organelles. Endomembranes fuse with and are removed from the plasma membrane by exocytosis and endocytosis, respectively.

PX domain

(Phox homology domain). A lipid and protein interaction domain that consists of 100–130 amino acids and is defined by sequences that are found in two components of the phagocyte NADPH oxidase (phox) complex.

Pleckstrin homology (PH) domain

A sequence of 100 amino acids that is present in many signalling molecules and binds to lipid products of phosphoinositide kinases.

EF hand

A protein motif that might bind to Ca2+.

Planar cell polarity

A one-dimensional polarity on a cell sheet that is essential for many aspects of the development of tissues.

Hereditary spastic paraplegia

A human progressive neuronal disease of hereditary origin that is characterized by increasing weakness and stiffness of the legs.

Laminary defect

A developmental defect of the brain that disorganizes the laminary structure of the cortex.

Long-term facilitation

A mode of synaptic plasticity in which stimulation results in a persistent increase in synaptic transmission.

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Hirokawa, N., Noda, Y., Tanaka, Y. et al. Kinesin superfamily motor proteins and intracellular transport. Nat Rev Mol Cell Biol 10, 682–696 (2009). https://doi.org/10.1038/nrm2774

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