Kinesins are a superfamily of microtubule-based motor proteins that have diverse functions in transport of vesicles, organelles and chromosomes, and regulate microtubule dynamics. There are 14 families of kinesins, all reprsented in humans. A standardized nomenclature was published in 2004 (Lawrence et al.).
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Nangaku M, Sato-Yoshitake R, Okada Y, Noda Y, Takemura R, Yamazaki H, Hirokawa N.; ''KIF1B, a novel microtubule plus end-directed monomeric motor protein for transport of mitochondria.''; PubMedEurope PMCScholia
Nislow C, Lombillo VA, Kuriyama R, McIntosh JR.; ''A plus-end-directed motor enzyme that moves antiparallel microtubules in vitro localizes to the interzone of mitotic spindles.''; PubMedEurope PMCScholia
Mayr MI, Hümmer S, Bormann J, Grüner T, Adio S, Woehlke G, Mayer TU.; ''The human kinesin Kif18A is a motile microtubule depolymerase essential for chromosome congression.''; PubMedEurope PMCScholia
Tokai N, Fujimoto-Nishiyama A, Toyoshima Y, Yonemura S, Tsukita S, Inoue J, Yamamota T.; ''Kid, a novel kinesin-like DNA binding protein, is localized to chromosomes and the mitotic spindle.''; PubMedEurope PMCScholia
Sekine Y, Okada Y, Noda Y, Kondo S, Aizawa H, Takemura R, Hirokawa N.; ''A novel microtubule-based motor protein (KIF4) for organelle transports, whose expression is regulated developmentally.''; PubMedEurope PMCScholia
Mazumdar M, Sundareshan S, Misteli T.; ''Human chromokinesin KIF4A functions in chromosome condensation and segregation.''; PubMedEurope PMCScholia
Cai S, Weaver LN, Ems-McClung SC, Walczak CE.; ''Kinesin-14 family proteins HSET/XCTK2 control spindle length by cross-linking and sliding microtubules.''; PubMedEurope PMCScholia
Navone F, Niclas J, Hom-Booher N, Sparks L, Bernstein HD, McCaffrey G, Vale RD.; ''Cloning and expression of a human kinesin heavy chain gene: interaction of the COOH-terminal domain with cytoplasmic microtubules in transfected CV-1 cells.''; PubMedEurope PMCScholia
Vale RD, Funatsu T, Pierce DW, Romberg L, Harada Y, Yanagida T.; ''Direct observation of single kinesin molecules moving along microtubules.''; PubMedEurope PMCScholia
Sindelar CV, Budny MJ, Rice S, Naber N, Fletterick R, Cooke R.; ''Two conformations in the human kinesin power stroke defined by X-ray crystallography and EPR spectroscopy.''; PubMedEurope PMCScholia
Okada Y, Yamazaki H, Sekine-Aizawa Y, Hirokawa N.; ''The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors.''; PubMedEurope PMCScholia
Espeut J, Gaussen A, Bieling P, Morin V, Prieto S, Fesquet D, Surrey T, Abrieu A.; ''Phosphorylation relieves autoinhibition of the kinetochore motor Cenp-E.''; PubMedEurope PMCScholia
Manning AL, Ganem NJ, Bakhoum SF, Wagenbach M, Wordeman L, Compton DA.; ''The kinesin-13 proteins Kif2a, Kif2b, and Kif2c/MCAK have distinct roles during mitosis in human cells.''; PubMedEurope PMCScholia
Brown CL, Maier KC, Stauber T, Ginkel LM, Wordeman L, Vernos I, Schroer TA.; ''Kinesin-2 is a motor for late endosomes and lysosomes.''; PubMedEurope PMCScholia
Hirokawa N, Noda Y.; ''Intracellular transport and kinesin superfamily proteins, KIFs: structure, function, and dynamics.''; PubMedEurope PMCScholia
Yang JT, Saxton WM, Stewart RJ, Raff EC, Goldstein LS.; ''Evidence that the head of kinesin is sufficient for force generation and motility in vitro.''; PubMedEurope PMCScholia
Wordeman L, Mitchison TJ.; ''Identification and partial characterization of mitotic centromere-associated kinesin, a kinesin-related protein that associates with centromeres during mitosis.''; PubMedEurope PMCScholia
Yang JT, Laymon RA, Goldstein LS.; ''A three-domain structure of kinesin heavy chain revealed by DNA sequence and microtubule binding analyses.''; PubMedEurope PMCScholia
Lawrence CJ, Dawe RK, Christie KR, Cleveland DW, Dawson SC, Endow SA, Goldstein LS, Goodson HV, Hirokawa N, Howard J, Malmberg RL, McIntosh JR, Miki H, Mitchison TJ, Okada Y, Reddy AS, Saxton WM, Schliwa M, Scholey JM, Vale RD, Walczak CE, Wordeman L.; ''A standardized kinesin nomenclature.''; PubMedEurope PMCScholia
Blangy A, Lane HA, d'Hérin P, Harper M, Kress M, Nigg EA.; ''Phosphorylation by p34cdc2 regulates spindle association of human Eg5, a kinesin-related motor essential for bipolar spindle formation in vivo.''; PubMedEurope PMCScholia
Kuznetsov SA, Vaisberg YA, Rothwell SW, Murphy DB, Gelfand VI.; ''Isolation of a 45-kDa fragment from the kinesin heavy chain with enhanced ATPase and microtubule-binding activities.''; PubMedEurope PMCScholia
Hammond JW, Cai D, Blasius TL, Li Z, Jiang Y, Jih GT, Meyhofer E, Verhey KJ.; ''Mammalian Kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition.''; PubMedEurope PMCScholia
Bloom GS, Wagner MC, Pfister KK, Brady ST.; ''Native structure and physical properties of bovine brain kinesin and identification of the ATP-binding subunit polypeptide.''; PubMedEurope PMCScholia
Mishima M, Kaitna S, Glotzer M.; ''Central spindle assembly and cytokinesis require a kinesin-like protein/RhoGAP complex with microtubule bundling activity.''; PubMedEurope PMCScholia
Kinesin-1 is a heterotetramer of two heavy chains (HCs) and two light chains (LCs). The HC tail binds microtubules and inhibits ATPase activity by interacting with the enzymatic HC heads. LCs regulate the head and microtubule-binding activities of the HC tail by reducing the affinity of the head-tail interaction over tenfold. By a separate mechanism LCs inhibit microtubule binding.
Kinesins consume ATP to power the motor which allows them to move along microtubules. The motor region contains highly conserved Switch 1 (SSRSH) and 2 (DLAGSE) motifs which change conformation during ATP hydrolysis (Rice et al. 1999). These form a salt-bridge that, in myosin, closes the nucleotide-binding cleft, enabling the motor to hydrolyze ATP (Geeves & Holmes 1999). This closed conformation has now been seen by cryo-electron microscopy in human conventional kinesin (Sindelar & Downing 2010) and in a crystal structure of the frog kinesin-5 Eg5 (Parke et al. 2010).
All kinesins contain a motor domain or head, the position varies but it is structurally highly conserved (Kull et al. 1996, Sablin et al. 1996). The microtubule-binding site includes structural elements which interact with tubulin and undergo movement between the ADP and ATP bound states. The highly conserved switch I (SSRSH) and II (DLAGSE) motifs, which change in conformation during the ATP hydrolysis cycle, form a salt-bridge that, in myosin, closes the nucleotide-binding cleft, enabling the motor to hydrolyze ATP (Geeves & Holmes 1999). This closed conformation has now been seen in a crystal structure of the frog kinesin-5 Eg5 (Parke et al. 2010).
Kinesin-5 motors are bipolar homotetramers with two motor domains at each end, separated by a stalk/tail region (Cole et al. 1994). During mitosis, Kinesin-5 motors function near the spindle midzone to maintain pole to pole distance. Motor domains attach to microtubules from opposite poles and translocate towards the plus ends, thereby pushing the spindle poles apart (Kapitein et al. 2005). Kinesin-5 is also involved in axon growth (Myers & Baas 2007).
Kinesin-8 is a plus-end-directed dimeric kinesin with an internal motor domain (Loughlin et al. 2008) that can depolymerize stable microtubuless specifically at their plus-ends (Pereira et al. 1997) in a length-dependent manner (Varga et al. 2006). Human kinesin-8 KIF18A is believed to promote chromosome congression by attenuating chromosome oscillation magnitudes (Stumpff et al. 2008).
Cytokinesis requires the central spindle, which forms during anaphase by the bundling of antiparallel nonkinetochore microtubules. Microtubule bundling and completion of cytokinesis require MKLP1, a kinesin-6 family member, and RACGAP1 (MgcRacGap), which contains a RhoGAP domain. These form a heterotetrameric complex known as centralspindlin. Centralspindlin, but not its individual components, strongly promotes microtubule bundling in vitro.
Chromokinesins consist of the kinesin-4 and kinesin-10 families.They act in various steps of mitosis, including chromosome condensation, metaphase alignment, chromosome segregation and cytokinesis (Mazumdar & Misteli 2005). Both families consist of homodimeric microtubule-based plus-end directed motor proteins (Sekine et al. 1994, Yajima et al. 2003).
Human kinesin-7, or CENP-E was one of the first kinesins to be discovered (Yen et al. 1991). It is essential for mammalian development, having a role in stabilizing kinetochore-microtubule capture (Putkey et al. 2002), CENP-E is an integral component of kinetochore corona fibers that link centromeres to spindle microtubules and localizes to kinetochores throughout all phases of mitotic chromosome movement (early premetaphase through anaphase A). Though originally reported to be minus-end-directed it is now believed to be a plus-end-directed dimeric kinesin (Espeut et al. 2008). It is sequestered in the cytoplasm until nuclear envelope breakdown and then localizes to its chromosomal cargo at the kinetochores (Brown et al. 1996).
Kinesin-2 is a heterotrimer with two different motor subunits and an accessory protein that is believed to interact with the cargo, or possibly regulate motor activity (Marszalek & Goldstein 2002). The motor domain interacts with microtubules and contains the ATPase used to translocate the holoenzyme along the microtubule. The coiled-coil stalk is where the two motor subunits interact with each other to form a stable heterodimer. The tail domains interact with the KAP3 non-motor accessory subunit. Kinesin-2 is a plus-end directed kinesin involved in photoreceptor cell function (Jimeno et al. 2006) and normal steady-state localization of late endosomes/lysosomes (Brown et al. 2005).
Kinesin-3 drives the transport of synaptic vesicle precursors to axon terminals. Loss of the Caenorhabditis elegans protein Unc104, eqivalent to human KIF1A, results in decreased synaptic vesicles in axonal growth cones. In mice loss of KIF1A caused severe motor and sensory abnormalities associated with neuronal cell death (Yonekawa et al. 1998). Kinesin-3 is often described as monomeric, but has recently been shown to be functionally dimeric (Hammond et al. 2009).
Kif15 (human kinesin-12) is by analogy with orthologous proteins believed to be a plus-end-directed motor. It cooperates with kinesin-5 to promote bipolar spindle assembly during cell division (Tanenbaum et al. 2009), with a mechanism that is distinct from that of kinesin-5 (Vanneste et al. 2009).
Kinesin-14 proteins have a C-terminal motor domain. At least four members of the group (Dm Ncd, Sc KAR3, Cg CHO2, At KCBP) have been demonstrated to be minus-end directed motors (Walker et al. 1990), in contrast to the usual plus-end directed motility of other kinesin proteins.
During spindle formation, Kinesin-14 cross-links antiparallel microtubules and slides them together (thereby generating inward forces) to balance the outward forces generated by plus-end-directed kinesins of the Kinesin-5 family. Kinesin-14 family members also gather microtubule minus-ends and focus them into spindle poles. Mutation or inhibition of Kinesin-14 family members often results in disordered or splayed meiotic spindle poles (Ambrose et al. 2005).
Kinesin-13 proteins are homodimeric with the kinesin motor in the middle of the amino acid sequence. They induce microtubule depolymerization by disassembling tubulin subunits from the polymer end (Desai et al. 1999).
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During spindle formation, Kinesin-14 cross-links antiparallel microtubules and slides them together (thereby generating inward forces) to balance the outward forces generated by plus-end-directed kinesins of the Kinesin-5 family. Kinesin-14 family members also gather microtubule minus-ends and focus them into spindle poles. Mutation or inhibition of Kinesin-14 family members often results in disordered or splayed meiotic spindle poles (Ambrose et al. 2005).