The Microtubule-Binding Protein Ensconsin Is an Essential Cofactor of Kinesin-1

Barlan, Kari; Lü, Wen; Gelfand, Vladimir I.

doi:10.1016/j.cub.2013.01.008

Cited by 130 publications

(155 citation statements)

References 25 publications

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“…In contrast to kinesin-1's function in streaming, dynein is not required for fast streaming; instead, it inhibits the shift from slow streaming to fast streaming (8,9). This KHC-dependent and KLC/dynein-independent streaming mechanism highly resembles another important function of KHC, called microtubule-microtubule sliding, studied by our group (10)(11)(12)(13)(14)(15). In this process, KHC binds one microtubule through its ATPindependent C-terminal-binding site while walking on another microtubule using its ATP-dependent motor domain, as reported by Winding et al (17).…”

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confidence: 60%

“…Cytoskeletal filaments and molecular motors are major players that generate the forces required for these activities. For instance, kinesin-1 and microtubules have been shown to provide the mechanical forces required in multiple cellular contexts, such as organelle transport (1)(2)(3)(4), ooplasmic streaming (5)(6)(7)(8)(9), and process formation (10)(11)(12)(13)(14)(15).…”

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confidence: 99%

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Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

Lü

Winding

Lakonishok

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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122

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Cytoplasmic streaming in Drosophila oocytes is a microtubulebased bulk cytoplasmic movement. Streaming efficiently circulates and localizes mRNAs and proteins deposited by the nurse cells across the oocyte. This movement is driven by kinesin-1, a major microtubule motor. Recently, we have shown that kinesin-1 heavy chain (KHC) can transport one microtubule on another microtubule, thus driving microtubule-microtubule sliding in multiple cell types. To study the role of microtubule sliding in oocyte cytoplasmic streaming, we used a Khc mutant that is deficient in microtubule sliding but able to transport a majority of cargoes. We demonstrated that streaming is reduced by genomic replacement of wild-type Khc with this sliding-deficient mutant. Streaming can be fully rescued by wild-type KHC and partially rescued by a chimeric motor that cannot move organelles but is active in microtubule sliding. Consistent with these data, we identified two populations of microtubules in fast-streaming oocytes: a network of stable microtubules anchored to the actin cortex and free cytoplasmic microtubules that moved in the ooplasm. We further demonstrated that the reduced streaming in sliding-deficient oocytes resulted in posterior determination defects. Together, we propose that kinesin-1 slides free cytoplasmic microtubules against cortically immobilized microtubules, generating forces that contribute to cytoplasmic streaming and are essential for the refinement of posterior determinants.kinesin-1 | microtubules | cytoplasmic streaming | Drosophila | axis determination

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confidence: 60%

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confidence: 99%

Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

Lü

Winding

Lakonishok

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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122

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“…To test whether the C-terminal MT-binding site of KHC is necessary for MT sliding, we assayed MT sliding using α-tubulin tagged with a tandem dimer of the photoconvertible probe EOS (tdEOS-tubulin) (9,19), which changes emission spectra from green to red upon exposure to UV light (20). To quantify MT sliding, we expressed tdEOS-tubulin in Drosophila S2 cells, photoconverted a small subset of MTs from green to red, and imaged converted MTs in the red channel.…”

Section: Significancementioning

confidence: 99%

Role of kinesin-1–based microtubule sliding in Drosophila nervous system development

Winding

Kelliher

Lü

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The plus-end microtubule (MT) motor kinesin-1 is essential for normal development, with key roles in the nervous system. Kinesin-1 drives axonal transport of membrane cargoes to fulfill the metabolic needs of neurons and maintain synapses. We have previously demonstrated that kinesin-1, in addition to its well-established role in organelle transport, can drive MT-MT sliding by transporting "cargo" MTs along "track" MTs, resulting in dramatic cell shape changes. The mechanism and physiological relevance of this MT sliding are unclear. In addition to its motor domain, kinesin-1 contains a second MT-binding site, located at the C terminus of the heavy chain. Here, we mutated this C-terminal MT-binding site such that the ability of kinesin-1 to slide MTs is significantly compromised, whereas cargo transport is unaffected. We introduced this mutation into the genomic locus of kinesin-1 heavy chain (KHC), generating the Khc mutA allele. Khc mutA neurons displayed significant MT sliding defects while maintaining normal transport of many cargoes. Using this mutant, we demonstrated that MT sliding is required for axon and dendrite outgrowth in vivo. Consistent with these results, Khc mutA flies displayed severe locomotion and viability defects. To test the role of MT sliding further, we engineered a chimeric motor that actively slides MTs but cannot transport organelles. Activation of MT sliding in Khc mutA neurons using this chimeric motor rescued axon outgrowth in cultured neurons and in vivo, firmly establishing the role of sliding in axon outgrowth. These results demonstrate that MT sliding by kinesin-1 is an essential biological phenomenon required for neuronal morphogenesis and normal nervous system development.kinesin-1 | microtubules | Drosophila | axon outgrowth | dendrite outgrowth N eurons are the basic unit of the nervous system, forming vast networks throughout the body that communicate using receptorligand machinery located in long cellular projections called axons and dendrites. Learning how these processes form is key to understanding the early development and pathology of the nervous system. Microtubules (MTs) and actin microfilaments have been implicated in neurite outgrowth, with many studies focusing on the growth cone at the tip of the axon. Previous models suggest that the driving forces for neurite outgrowth are MT polymerization and the treadmilling of F-actin (1, 2). However, other studies demonstrate that F-actin is dispensable to outgrowth and neurites extend even in the absence of F-actin (3-5).Our group has found that the motor protein kinesin-1 can rearrange the MT network by sliding MTs against each other (6). We have shown that kinesin-1 is required for MT sliding in cultured neurons and kinesin-1 depletion inhibits both neurite outgrowth and regeneration (7,8). Additionally, we have observed MT sliding in axons as well as MTs pushing on the axon tip (9). Recent studies from other groups have also implicated MT translocation in axon extension and dendritic organization (10-12). Based on th...

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“…Defects in spermatogenesis Komada et al (2000), Sung et al (2008), Barlan et al (2013), and Metzger et al (2012) Reduced viability (in Drosophila) Myonuclear positioning altered (in Drosophila)…”

Section: Map6mentioning

confidence: 99%

“…It has also been demonstrated to be a regulator of kinesin motors. MAP7 is a cofactor of kinesin-1 and required for organelle transport in Drosophila neurons (Barlan et al 2013). MAP7 mutants display defects in motor localization without altering MT cytoskeleton (Sung et al 2008).…”

Section: Map7 Family Of Microtubule-associated Proteinsmentioning

confidence: 99%

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

2016

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Dendrites have a unique microtubule organization. In vertebrates, dendritic microtubules are organized in antiparallel bundles, oriented with their plus ends either pointing away or toward the soma. The mixed microtubule arrays control intracellular trafficking and local signaling pathways, and are essential for dendrite development and function. The organization of microtubule arrays largely depends on the combined function of different microtubule regulatory factors or generally named microtubule-associated proteins (MAPs). Classical MAPs, also called structural MAPs, were identified more than 20 years ago based on their ability to bind to and copurify with microtubules. Most classical MAPs bind along the microtubule lattice and regulate microtubule polymerization, bundling, and stabilization. Recent evidences suggest that classical MAPs also guide motor protein transport, interact with the actin cytoskeleton, and act in various neuronal signaling networks. Here, we give an overview of microtubule organization in dendrites and the role of classical MAPs in dendrite development, dendritic spine formation, and synaptic plasticity. IntroductionMicrotubules (MTs) are cytoskeletal structures that play essential roles in all eukaryotic cells. MTs are important not only during cell division but also in non-dividing cells, where they are critical structures in numerous cellular processes such as cell motility, migration, differentiation, intracellular transport and organelle positioning. MTs are composed of two proteins, α-and β-tubulin, that form heterodimers and organize themselves in a head-to-tail manner. MTs are dynamic and they can rapidly switch between cycles of growth and shrinkage. This MT

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The Microtubule-Binding Protein Ensconsin Is an Essential Cofactor of Kinesin-1

Cited by 130 publications

References 25 publications

Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

Microtubule–microtubule sliding by kinesin-1 is essential for normal cytoplasmic streaming in Drosophila oocytes

Role of kinesin-1–based microtubule sliding in Drosophila nervous system development

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

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