Kinesin-1 regulates dendrite microtubule polarity in Caenorhabditis elegans

Yan, Junkai; Chao, Dan L; Toba, Shiori; Koyasako, Kotaro; Yasunaga, Takuo; Hirotsune, Shinji; Shen, Kang

doi:10.7554/elife.00133

Cited by 115 publications

(170 citation statements)

References 53 publications

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“…Importantly, the ability of KHC mutA to bind many cargo adapters and transport cargoes was similar to wild-type KHC. This finding is in agreement with a study in Caenorhabditis elegans, which demonstrated that a similar mutation in the C-terminal MT-binding site of kinesin-1 did not affect mitochondria transport (11).…”

Section: Discussionsupporting

confidence: 82%

“…Khc mutA larvae display reduced dendritic branching and total dendrite length in class I and IV da neurons, suggesting that MT sliding is important for arborization. This result is consistent with a previous study in C. elegans, where the authors demonstrate that mutations in the C terminus of the kinesin-1 ortholog, unc-116, result in dendritic phenotypes in vivo (11). A unc-116 truncation mutant lacking the C terminus, including the MT-binding site, displayed axon-like MT polarity in dendrites, as well as mislocalization of axonal cargoes to dendrites.…”

Section: Discussionsupporting

confidence: 82%

“…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)(11)(12). Based on these studies, we hypothesize that kinesin-1 drives neurite extension by sliding MTs against the plasma membrane.…”

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confidence: 81%

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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.

106

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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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Section: Discussionsupporting

confidence: 82%

Section: Discussionsupporting

confidence: 82%

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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.

106

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“…Motor proteins either anchored to the cell cortex or spanning two microtubules can facilitate the sliding of preassembled microtubules from the soma into the dendrite. 6,25 In addition, as the dendrite arbor elaborates and after it reaches the mature state, microtubule motor proteins maintain and enhance the minus-end distal population by selectively removing plus-end distal microtubules 30 and guiding new polymerization events passing through dendrite branch points in the retrograde direction. 31 A second mechanism is via the nucleation of microtubules, i.e., de novo initiation of microtubule polymerization within a nascent dendrite branch.…”

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confidence: 99%

Microtubule nucleation and organization in dendrites

2016

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“…It has been suggested that the minus-end out MT organization in neurons is maintained by steering of polymerizing MTs along the stable MTs by kinesin-2 motors bound to growing MT plus ends Doodhi et al 2014). Other motor proteins, such as kinesin-1, might also be able to crosslink antiparalleled MTs and are critical in forming the characteristic minus-end out MT organization of C. elegans dendrites (Yan et al 2013).…”

Section: Organization Of Axonal and Dendritic Microtubulesmentioning

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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Kinesin-1 regulates dendrite microtubule polarity in Caenorhabditis elegans

Cited by 115 publications

References 53 publications

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

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

Microtubule nucleation and organization in dendrites

Microtubule Organization and Microtubule-Associated Proteins (MAPs)

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