The tubulin code and its role in controlling microtubule properties and functions

Nature Reviews Molecular Cell Biology, Год журнала: 2020, Номер 21(6), С. 307 - 326

Опубликована: Фев. 27, 2020

Язык: Английский

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Microtubule-Associated Proteins: Structuring the Cytoskeleton

Trends in Cell Biology, Год журнала: 2019, Номер 29(10), С. 804 - 819

Опубликована: Авг. 12, 2019

Язык: Английский

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Structural and functional insight into regulation of kinesin-1 by microtubule-associated protein MAP7

Science, Год журнала: 2022, Номер 375(6578), С. 326 - 331

Опубликована: Янв. 20, 2022

Microtubule (MT)-associated protein 7 (MAP7) is a required cofactor for kinesin-1-driven transport of intracellular cargoes. Using cryo-electron microscopy and single-molecule imaging, we investigated how MAP7 binds MTs facilitates kinesin-1 motility. The MT-binding domain (MTBD) bound as an extended α helix between the protofilament ridge site lateral contact. Unexpectedly, MTBD partially overlapped with binding inhibited its However, by tethering to MT, projection prevented dissociation motor facilitated available neighboring sites. inhibitory effect dominated became saturated MAP7. Our results reveal biphasic regulation in context their competitive MTs.

Язык: Английский

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TRAK adaptors regulate the recruitment and activation of dynein and kinesin in mitochondrial transport

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Март 13, 2023

Mitochondrial transport along microtubules is mediated by Miro1 and TRAK adaptors that recruit kinesin-1 dynein-dynactin. To understand how these opposing motors are regulated during mitochondrial transport, we reconstitute the bidirectional of Miro1/TRAK in vitro. We show coiled-coil domain activates dynein-dynactin enhances motility activated its cofactor MAP7. find both move towards kinesin-1's direction, whereas excluded from binding transported dynein-dynactin, avoiding motor tug-of-war. also test predictions models explain stalls regions with elevated Ca2+. Transport not affected Instead, demonstrate microtubule docking protein syntaphilin induces resistive forces stall dynein-driven motility. Our results suggest Ca2+-mediated recruitment to membrane, disruption machinery.

Язык: Английский

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MAP7 family proteins regulate kinesin-1 recruitment and activation

The Journal of Cell Biology, Год журнала: 2019, Номер 218(4), С. 1298 - 1318

Опубликована: Фев. 15, 2019

Kinesin-1 is responsible for microtubule-based transport of numerous cellular cargoes. Here, we explored the regulation kinesin-1 by MAP7 proteins. We found that all four mammalian family members bind to kinesin-1. In HeLa cells, MAP7, MAP7D1, and MAP7D3 act redundantly enable kinesin-1–dependent microtubule recruitment truncated KIF5B-560, which contains stalk but not cargo-binding autoregulatory regions. vitro, purified increase landing rate processivity through transient association with motor. proteins promote binding microtubules both directly, N-terminal microtubule-binding domain unstructured linker region, indirectly, an allosteric effect exerted kinesin-binding C-terminal domain. Compared has a higher affinity lower and, unlike can be cotransported propose are microtubule-tethered activators, motor transiently interacts as it moves along microtubules.

Язык: Английский

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A Combinatorial MAP Code Dictates Polarized Microtubule Transport

Developmental Cell, Год журнала: 2020, Номер 53(1), С. 60 - 72.e4

Опубликована: Фев. 27, 2020

Язык: Английский

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Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport

The EMBO Journal, Год журнала: 2018, Номер 37(23)

Опубликована: Ноя. 12, 2018

Язык: Английский

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Tau: It’s Not What You Think

Trends in Cell Biology, Год журнала: 2019, Номер 29(6), С. 452 - 461

Опубликована: Март 28, 2019

Язык: Английский

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

Journal of Cellular Physiology, Год журнала: 2018, Номер 234(6), С. 7923 - 7937

Опубликована: Дек. 10, 2018

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

Язык: Английский

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Synergistic autoinhibition and activation mechanisms control kinesin-1 motor activity

Cell Reports, Год журнала: 2022, Номер 39(9), С. 110900 - 110900

Опубликована: Май 1, 2022

Kinesin-1 activity is regulated by autoinhibition. Intramolecular interactions within the kinesin heavy chain (KHC) are proposed to be one facet of motor regulation. The KHC also binds light (KLC), which has been implicated in both autoinhibition and activation motor. We show that KLC inhibits kinesin-microtubule interaction independently from intramolecular KHC. Cargo-adaptor proteins bind stimulated processive movement, but landing rate activated complexes remained low. Microtubule-associated protein 7 (MAP7) enhanced motility increasing run length motors. Our results support a model whereby synergistic inhibition mechanisms cargo-adaptor binding releases mechanisms. However, non-motor MAP required for robust microtubule association Thus, human

Язык: Английский

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