A Combinatorial MAP Code Dictates Polarized Microtubule Transport

Monroy, Brigette Y.; Tan, Tracy; Oclaman, Janah May; Han, Jisoo S.; Simó, Sergi; Niwa, Shinsuke; Nowakowski, Dan W.; McKenney, Richard J.; Ori-McKenney, Kassandra M.

doi:10.1016/j.devcel.2020.01.029

Cited by 127 publications

(173 citation statements)

References 88 publications

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“…Thus, we find that Tau binds preferentially along MT shafts but not at plus ends, whereas Eb1 binds in complementary fashion and displays elevated shaft binding when Tau is absent ( Fig.5C and 7D'). Such competitive binding behaviour is reminiscent of Tau's role in preventing MAP6 from binding in certain regions of the MT lattice (Baas & Qiang, 2019, Qiang et al, 2018; it is in agreement with the idea of a MAP code where similar MAP competition is assumed to regulate regionspecific axonal transport (Monroy, Tan et al, 2020).…”

Section: Eb1 and Xmap215/msps Are Core Factors Promoting Mt Polymerissupporting

confidence: 75%

Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons

Hahn

Voelzmann

Parkin

et al. 2020

Preprint

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Axons are the enormously long cable-like cellular processes of neurons that wire nervous systems and have to survive for up to a century in humans. We lose ~40% of axons towards high age and far more in neurodegenerative diseases. Sustaining axons requires axonal transport and dynamic morphogenetic changes, both crucially dependent on bundles of microtubules that run all along axons. How polymerisation is regulated to form, repair and replace microtubules in these bundles during axon development and maintenance is virtually unknown. Here, we show in axons of Drosophila and Xenopus neurons alike that Eb1, XMAP215/Msps and Tau are key players which operate as one functional unit to promote microtubule polymerisation. Eb1 and XMAP215/Msps are interdependent core factors at the microtubule tip, whereas Tau outcompetes Eb1 binding at microtubule lattices, thus preventing its pool depletion at polymerising plus ends. In agreement with their closely interwoven functions, the three factors show the same combination of axonal loss-of-function mutant phenotypes including: (1) reduced microtubule polymerisation dynamics and shorter axon growth, indicating their importance for upholding microtubule mass in axons; (2) prominent deterioration of parallel microtubule bundles into disorganised curled conformations, indicating their key roles in promoting essential axonal architecture. We show the latter to occur through Eb1- and spectraplakin-dependent guidance of extending microtubules. We conclude that Eb1, XMAP215/Msps and Tau jointly promote microtubule polymerisation, important to regulate the quantity and bundled organisation of microtubules and offering new ways to think about developmental and degenerative axon pathologies and how to treat them.

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Section: Eb1 and Xmap215/msps Are Core Factors Promoting Mt Polymerissupporting

confidence: 75%

Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons

Hahn

Voelzmann

Parkin

et al. 2020

Preprint

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“…1 A, ii; Gumy et al, 2017;van Beuningen et al, 2015). These proteins may represent a staggered PAEZ/AIS-like filter system (see above), since MAP2 is required to block somatic organelles from entering DRG axons; in addition, MAP2 selectively activates kinesin-mediated transport, in line with a recently proposed "MAP code" for the regulation of polarized MT-based traffic (Gumy et al, 2017;Monroy et al, 2020); these roles of MAP2 demonstrated at stem axons may similarly contribute to PAEZ filter functions at the axon hillock. Outside the stem axon, vertebrate sensory neurons likely have further filter zones ( Fig.…”

Section: Do Ais Features Apply To Other Neuron Classes?mentioning

confidence: 72%

Cytoskeletal organization of axons in vertebrates and invertebrates

Prokop

2020

Journal of Cell Biology

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The maintenance of axons for the lifetime of an organism requires an axonal cytoskeleton that is robust but also flexible to adapt to mechanical challenges and to support plastic changes of axon morphology. Furthermore, cytoskeletal organization has to adapt to axons of dramatically different dimensions, and to their compartment-specific requirements in the axon initial segment, in the axon shaft, at synapses or in growth cones. To understand how the cytoskeleton caters to these different demands, this review summarizes five decades of electron microscopic studies. It focuses on the organization of microtubules and neurofilaments in axon shafts in both vertebrate and invertebrate neurons, as well as the axon initial segments of vertebrate motor- and interneurons. Findings from these ultrastructural studies are being interpreted here on the basis of our contemporary molecular understanding. They strongly suggest that axon architecture in animals as diverse as arthropods and vertebrates is dependent on loosely cross-linked bundles of microtubules running all along axons, with only minor roles played by neurofilaments.

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“…Next, we set out to investigate the spatial regulation of the activity of the kinesins associated with Rab6 vesicles. Previous work has shown that KIF5B depends on the members of MAP7 family for its activation (Hooikaas et al, 2019;Metzger et al, 2012;Monroy et al, 2018;Pan et al, 2019), while kinesin-3 is inhibited by MAP7 (Monroy et al, 2018;Monroy et al, 2020).…”

Section: Combination Of Kif5b and Kif13b Allows Rab6 Vesicles To Reacmentioning

confidence: 99%

Concerted action of kinesins KIF5B and KIF13B promotes efficient secretory vesicle transport to microtubule plus ends

Serra-Marques

Martin

Katrukha

et al. 2020

Preprint

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Intracellular transport relies on different types of kinesins, but it is poorly understood which kinesins are present on a particular cargo, what their specific roles are and whether they can act simultaneously on the same cargo. Here, we show that Rab6-positive secretory vesicles are transported from the Golgi apparatus to the cell periphery by kinesin-1 KIF5B and kinesin-3 KIF13B, which determine the location of secretion events. KIF5B plays a dominant role, whereas KIF13B helps Rab6 vesicles to reach freshly polymerized microtubule ends, to which KIF5B binds poorly, likely because its cofactors, MAP7-family proteins, are slow in populating these ends. Sub-pixel localization demonstrated that during microtubule plusend directed transport, both kinesins localize to the vesicle front and can be engaged on the same vesicle. When vesicles reverse direction, KIF13B relocates to the middle of the vesicle, while KIF5B shifts to the back, suggesting that KIF5B but not KIF13B undergoes a tug-of-war with a minus-end directed motor.

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A Combinatorial MAP Code Dictates Polarized Microtubule Transport

Cited by 127 publications

References 88 publications

Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons

Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons

Cytoskeletal organization of axons in vertebrates and invertebrates

Concerted action of kinesins KIF5B and KIF13B promotes efficient secretory vesicle transport to microtubule plus ends

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