KINESIN-2 Motors Adapt their Stepping Behavior for Processive Transport on Axonemes and Microtubules

Stepp, Willi L.; Merck, Georg; Mueller-Planitz, Felix; Ökten, Zeynep

doi:10.1016/j.bpj.2017.11.2792

Cited by 8 publications

(11 citation statements)

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“…Given an average train size of $200 nm [32], up to $20 active kinesin-2 head domains thus ''line up'' along the train, with close spacing between dimers. Moreover, these kinesin-2 motors use the B-tubule of the axoneme, which prevents head-on collisions with retrograde trains moving along the A-tubule [32,33]. Such specialized transport geometry raises the question of how the assembled head domains on each train coordinate their actions to achieve efficient IFT in vivo (Figure 1).…”

Section: Resultsmentioning

confidence: 99%

Kinesin-2 from C. reinhardtii Is an Atypically Fast and Auto-inhibited Motor that Is Activated by Heterotrimerization for Intraflagellar Transport

et al. 2020

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Section: Resultsmentioning

confidence: 99%

Kinesin-2 from C. reinhardtii Is an Atypically Fast and Auto-inhibited Motor that Is Activated by Heterotrimerization for Intraflagellar Transport

et al. 2020

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“…Yet unlike other processive kinesins, KIF3AB's motility is highly sensitive to hindering loads resulting in detachment at low stall forces (43,44). This property is encoded in the catalytic motor domains rather than the neck linker or coiled-coil, and has physiological implications in that in vivo, the detachment of KIF3AB-KAP under load may serve as a mechanism to navigate roadblocks, sidestep to another microtubule track, and/or regulate IFT particle transport for ciliary tip length control and structure (45)(46)(47)(48).…”

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confidence: 99%

Kinesin-2 heterodimerization alters entry into a processive run along the microtubule but not stepping within the run

Quinn¹,

Howsmon

Hahn

et al. 2018

Journal of Biological Chemistry

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Keywords: computational biology, intracellular trafficking, intraflagellar transport, ciliogenesis, mathematical modeling, microtubule, neuron, presteady-state kinetics, ATPase, processivity ABSTRACTHeterodimeric KIF3AC and KIF3AB, two members of the mammalian kinesin-2 family, generate force for microtubule plus end-directed cargo transport. However, the advantage of heterodimeric kinesins over homodimeric ones is not well understood. We showed previously that microtubule association for entry into a processive run was similar in rate for KIF3AC and KIF3AB at ~7.0 µM -1 s -1 . Yet, for engineered homodimers of KIF3AA and KIF3BB, this constant is significantly faster at 11 µM -1 s -1 and much slower for KIF3CC at 2.1 µM -1 s -1. These results led us to hypothesize that heterodimerization of KIF3A with KIF3C and KIF3A with KIF3B altered the intrinsic catalytic properties of each motor domain. Here, we tested this hypothesis by using presteady-state stoppedflow kinetics and mathematical modeling. Surprisingly, the modeling revealed that the catalytic properties of KIF3A and KIF3B/C were altered upon microtubule binding, yet each motor domain retained its relative intrinsic kinetics for ADP release and subsequent ATP binding and the nucleotide-promoted transitions thereafter. These results are consistent with the interpretation that for KIF3AB, each motor head is catalytically similar and therefore each step is approximately equivalent. In contrast, for KIF3AC the results predict that the processive steps will alternate between a fast step for KIF3A followed by a slow step for KIF3C resulting in asymmetric stepping during a processive run. This study reveals the impact of heterodimerization of the motor polypeptides for microtubule association to start the processive run and the fundamental differences in the motile properties of KIF3C in comparison to KIF3A and KIF3B.Kinesin-2 is a unique family of processive kinesins because it contains both homodimeric and heterodimeric motors involved in microtubule plusend directed cargo transport (reviewed in (1-4)). The mammalian heterodimeric kinesins result from three gene products: KIF3A, KIF3B, and KIF3C to form heterodimeric . KIF3AB and its orthologs form a heterotrimeric complex by association with KAP, a distinctive http://www.jbc.org/cgi/doi/10.1074/jbc.RA118.002767 The latest version is at JBC Papers in Press. Published on July 10, 2018 as Manuscript RA118.002767 by guest on April 27, 2019 http://www.jbc.org/ Downloaded from 2 adaptor protein for cargo linkage because it is largely composed of armadillo repeats (10)(11)(12)(13)(14)(15). It is the armadillo repeats that provide specificity of the interaction between KIF3AB and KAP and between KIF3AB-KAP and its cargo. KIF3AB-KAP transports multimeric protein complexes (designated intraflagellar transport (IFT) particles) into the cilium and has also been linked to ciliadependent signal transduction pathways including the Hedgehog signaling pathway (16,17). Moreover, KIF3A, KIF3B, and KAP are all essential genes (18)...

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“…Motor proteins can move MT relative to one another which allows spindle formation in the absence of centrosomes in conditions such as during female meiosis or when the centrosome is disabled genetically or ablated by laser (Borisy et al, 2016). In higher eukaryotes, kinesin-2 acts on MT in the cytoplasm (Stepp, Merck, Mueller-planitz, & Ökten, 2017). Nucleation of MT from an organizing center develops radially in all directions.…”

Section: Mt-associated Proteins and Motor Proteins Regulate Mt Dynamicsmentioning

confidence: 99%

Microtubules: From understanding their dynamics to using them as potential therapeutic targets

Ilan

2018

Journal Cellular Physiology

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Microtubules (MT) and actin microfilaments are dynamic cytoskeleton components involved in a range of intracellular processes. MTs play a role in cell division, beating of cilia and flagella, and intracellular transport. Over the past decades, much knowledge has been gained regarding MT function and structure, and its role in underlying disease progression. This makes MT potential therapeutic targets for various disorders. Disturbances in MT and their associated proteins are the underlying cause of diseases such as Alzheimer’s disease, cancer, and several genetic diseases. Some of the advances in the field of MT research, as well as the potenti G beta gamma, is needed al uses of MT‐targeting agents in various conditions have been reviewed here.

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KINESIN-2 Motors Adapt their Stepping Behavior for Processive Transport on Axonemes and Microtubules

Cited by 8 publications

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Kinesin-2 from C. reinhardtii Is an Atypically Fast and Auto-inhibited Motor that Is Activated by Heterotrimerization for Intraflagellar Transport

Kinesin-2 from C. reinhardtii Is an Atypically Fast and Auto-inhibited Motor that Is Activated by Heterotrimerization for Intraflagellar Transport

Kinesin-2 heterodimerization alters entry into a processive run along the microtubule but not stepping within the run

Microtubules: From understanding their dynamics to using them as potential therapeutic targets

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