ReMAPping the microtubule landscape: How phosphorylation dictates the activities of microtubule‐associated proteins

Ramkumar, Amrita; Jong, Brigette Y; Ori-McKenney, Kassandra M.

doi:10.1002/dvdy.24599

Cited by 151 publications

(120 citation statements)

References 324 publications

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“…Barisic et al, 2015). At the entry into mitosis, cyclin-dependent kinase 1 (CDK1) is activated and triggers a cascade of phosphorylation events that ultimately regulate the activity of MAPs and motors (Cassimeris, 1999; Ramkumar, Jong, & Ori-McKenney, 2018). The functional shift of this complex machinery leads to the reconfiguration of the MT landscape in mitosis and thus requires specific methodologies to investigate the implications of tubulin PTMs during this process.…”

Section: Introductionmentioning

confidence: 99%

Dissecting the role of the tubulin code in mitosis

Ferreira

Figueiredo

Orr

et al. 2018

Methods in Cell Biology

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Mitosis is an essential process that takes place in all eukaryotes and involves the equal division of genetic material from a parental cell into two identical daughter cells. During mitosis, chromosome movement and segregation are orchestrated by a specialized structure known as the mitotic spindle, composed of a bipolar array of microtubules. The fundamental structure of microtubules comprises of α/β-tubulin heterodimers that associate head-to-tail and laterally to form hollow filaments. In vivo, microtubules are modified by abundant and evolutionarily conserved tubulin posttranslational modifications (PTMs), giving these filaments the potential for a wide chemical diversity. In recent years, the concept of a "tubulin code" has emerged as an extralayer of regulation governing microtubule function. A range of tubulin isoforms, each with a diverse set of PTMs, provides a readable code for microtubule motors and other microtubule-associated proteins. This chapter focuses on the complexity of tubulin PTMs with an emphasis on detyrosination and summarizes the methods currently used in our laboratory to experimentally manipulate these modifications and study their impact in mitosis.

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Section: Introductionmentioning

confidence: 99%

Dissecting the role of the tubulin code in mitosis

Ferreira

Figueiredo

Orr

et al. 2018

Methods in Cell Biology

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“…In Drosophila, the kinesin-1 sliding is counteracted by the "mitotic" kinesin MKLP1 (Del Castillo et al, 2015), which potentially cross-links microtubules. In mammalian neurons, the stabilization of microtubule cytoskeleton relies on various MAPs that can bind and stabilize individual microtubules and cross-link them together (Ramkumar et al, 2018). This is especially apparent in the axon, where the microtubules are regularly spaced and accumulate modifications indicative for long lived microtubules (Chen et al, 1992;Song and Brady, 2015).…”

Section: Discussionmentioning

confidence: 99%

Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity and functioning

Kooistra

Das

et al. 2019

Preprint

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Neurons are among the most highly polarized cell types. They possess structurally and functionally different processes, axon and dendrites, to mediate information flow through the nervous system.Although it is well known that the microtubule cytoskeleton has a central role in establishing neuronal polarity, how its specific organization is established and maintained is little understood.Using the in vivo model system Caenorhabditis elegans, we found that the highly conserved UNC-119 protein provides a link between the membrane-associated Ankyrin (UNC-44) and the microtubuleassociated CRMP (UNC-33). Together they form a periodic membrane-associated complex that anchors axonal and dendritic microtubule bundles to the cell cortex. This anchoring is critical to maintain microtubule organization by opposing kinesin-1 powered microtubule sliding. Disturbing this molecular complex alters neuronal polarity and causes strong developmental defects of the nervous system leading to severely paralyzed animals.

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“…MAPs regulate microtubule dynamics and organization (8)(9)(10). MAPs also control the interface between motor proteins and the microtubule surface to regulate motility.…”

Section: Introductionmentioning

confidence: 99%

MAP7 recruits kinesin-1 to microtubules to direct organelle transport

Chaudhary

Krementsova

et al. 2019

Preprint

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Microtubule-associated proteins (MAPs) play wellcharacterized roles in regulating microtubule polymerization, dynamics, and organization. In addition, MAPs control transport along microtubules by regulating the motility of kinesin and dynein. MAP7 (ensconsin, E-MAP-115) is a ubiquitous MAP that organizes the microtubule cytoskeleton in mitosis and neuronal branching. MAP7 also promotes the interaction of kinesin-1 with microtubules. We expressed and purified full-length kinesin-1 and MAP7 in Sf9 cells. In single-molecule motiity assays, MAP7 recruits kinesin-1 to microtubules, increasing the frequency of both diffusive and processive runs. Optical trapping assays on beads transported by single and teams of kinesin-1 motors indicate that MAP7 increases the relative binding rate of kinesin-1 and the number of motors simultaneously engaged in ensembles. To examine the role of MAP7 in regulating bidirectional transport, we isolated late phagosomes along with their native set of kinesin-1, kinesin-2, and dynein motors. Bidirectional cargoes exhibit a clear shift towards plus-end directed motility on MAP7-decorated microtubules due to increased forces exerted by kinesin teams. Collectively, our results indicate that MAP7 enhances kinesin-1 recruitment to microtubules and targets organelle transport to the plus end. Intracellular transport | MAP7 | Optical tweezers | kinesin-1 | kinesin-2 | dynein | in vitro reconstitutionCorrespondence: adam.hendricks @mcgill.ca

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ReMAPping the microtubule landscape: How phosphorylation dictates the activities of microtubule‐associated proteins

Cited by 151 publications

References 324 publications

Dissecting the role of the tubulin code in mitosis

Dissecting the role of the tubulin code in mitosis

Cortical anchoring of the microtubule cytoskeleton is essential for neuron polarity and functioning

MAP7 recruits kinesin-1 to microtubules to direct organelle transport

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