Intracellular cargo transport by kinesin-3 motors

Siddiqui, Nida; Straube, Anne

doi:10.1134/s0006297917070057

Cited by 59 publications

(87 citation statements)

References 133 publications

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“…In part analogously, the constitutively dimeric kinesin-14 molecules, diffusing along microtubules via their tail anchoring domain, become activated upon binding of a second microtubule, to which they crosslink, and which they then actively slide [6,7]. By contrast, Kif14 is activated, like other kinesin-3 family members [15,[44][45][46], by dimerization. Once activated, Kif14 molecules can walk processively as individual molecules.…”

Section: Discussionmentioning

confidence: 99%

Intrinsically disordered domain of kinesin-3 Kif14 enables unique functional diversity

Zhernov

Diez

Braun

et al. 2020

Preprint

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In addition to their force-generating motor domains, kinesin motor proteins feature various accessory domains enabling them to fulfil a variety of functions in the cell. Human kinesin-3, Kif14, localizes to the midbody of the mitotic spindle and is involved in the progression of cytokinesis. The specific motor properties enabling Kif14's cellular functions, however, remain unknown. Here, we show in vitro that it is the intrinsically disordered N-terminal domain of Kif14 that enables unique functional diversity of the motor. Using single molecule TIRF microscopy we observed that the presence of the disordered domain i) increased the Kif14 run-length by an order of magnitude, rendering the motor super-processive and enabling the motor to pass through highly crowded microtubule areas shielded by cohesive layers of microtubule-associated protein tau, which blocks less processive motors ii) enabled robust, autonomous Kif14 tracking of growing microtubule tips, independent of microtubule end-binding (EB) proteins and iii) enabled Kif14 to crosslink parallel microtubules and to drive the relative sliding of antiparallel ones. We explain these features of Kif14 by the observed increased affinity of the disordered domain for GTP-like tubulin and the observed diffusible interaction of the disordered domain with the microtubule lattice. We hypothesize that the disordered domain tethers the motor domain to the microtubule forming a diffusible foothold. We suggest that the intrinsically disordered N-terminal anchoring domain of Kif14 is a regulatory hub supporting the various cellular functions of Kif14 by tuning the motor's interaction with microtubules.

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Section: Discussionmentioning

confidence: 99%

Intrinsically disordered domain of kinesin-3 Kif14 enables unique functional diversity

Zhernov

Diez

Braun

et al. 2020

Preprint

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“…The activation of calpain has been shown to degrade microtubule-associated proteins (MAPs), which are a large family of proteins that function to regulate formation and organization of microtubules (Maccioni & Cambiazo, 1995;Springer, Azbill, Kennedy, George, & Geddes, 1997). In the axon of neurons, microtubules function to facilitate the transportation of various cargoes by kinesin (Siddiqui & Straube, 2017). As axons transport materials across their elongated structure, this microtubule degradation and dysregulation impairs this transport (Park et al, 2013).…”

Section: Mechanoporationmentioning

confidence: 99%

The overlooked aspect of excitotoxicity: Glutamate‐independent excitotoxicity in traumatic brain injuries

Tehse

Taghibiglou

2019

Eur J of Neuroscience

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Traumatic brain injury (TBI) is a leading major cause of morbidity and mortality in youth and individuals under 45 year age. A wide variety of cellular and molecular mechanisms have been identified contributing to the pathogenesis of TBI. A better understanding of the pathophysiology behind TBI is essential for providing more effective treatment. Excitotoxicity as one of the secondary molecular events is a major contributing factor in apoptosis and neuronal death following the initial injury in TBI. Excitotoxicity is the rapid overload and influx of calcium into the cell cytoplasm, activating a series of deleterious signaling cascades causing the cell to undergo apoptosis. Conventional understanding is that the rapid influx of calcium is initiated through glutamate release. However, there are overlooked glutamate‐independent mechanisms that cause the rapid calcium influx into the neuronal cytoplasm, evoking or contributing to excitotoxicity. Therefore, the focus of this review will be on the role of the glutamate‐independent excitotoxic mechanisms of the mechanosensitive response of NMDA receptors, mechanoporation of the cell membrane, ischemia, and the release of calcium from intracellular stores. In conclusion, the shear and stretch forces during a TBI event may result in the mechanosensitive activation of NMDA receptors which contribute to glutamate‐independent excitotoxicity.

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“…Kinesin‐3 motors are MT plus end‐directed motors that are thought to have been present in the last common eukaryotic ancestor (LCEA), but are absent from present day land plants . The founding member of the kinesin‐3 family is Unc‐104 from C. elegans , which mediates axonal transport of synaptic vesicles in C. elegans .…”

Section: Trafficking Of Membrane Proteins Into and Out Of The Primarymentioning

confidence: 99%

Regulation of ciliary membrane protein trafficking and signalling by kinesin motor proteins

2018

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Primary cilia are antenna-like sensory organelles that regulate a substantial number of cellular signalling pathways in vertebrates, both during embryonic development as well as in adulthood, and mutations in genes coding for ciliary proteins are causative of an expanding group of pleiotropic diseases known as ciliopathies. Cilia consist of a microtubule-based axoneme core, which is subtended by a basal body and covered by a bilayer lipid membrane of unique protein and lipid composition. Cilia are dynamic organelles, and the ability of cells to regulate ciliary protein and lipid content in response to specific cellular and environmental cues is crucial for balancing ciliary signalling output. Here we discuss mechanisms involved in regulation of ciliary membrane protein trafficking and signalling, with main focus on kinesin-2 and kinesin-3 family members.

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Intracellular cargo transport by kinesin-3 motors

Cited by 59 publications

References 133 publications

Intrinsically disordered domain of kinesin-3 Kif14 enables unique functional diversity

Intrinsically disordered domain of kinesin-3 Kif14 enables unique functional diversity

The overlooked aspect of excitotoxicity: Glutamate‐independent excitotoxicity in traumatic brain injuries

Regulation of ciliary membrane protein trafficking and signalling by kinesin motor proteins

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