MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport

Tymanskyj, Stephen R.; Yang, Benjamin; Verhey, Kristen J.; Ma, Le

doi:10.7554/elife.36374

Cited by 60 publications

(88 citation statements)

References 57 publications

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“…The modification could either directly affect the efficiency of the molecular motors, such as kinesins and dynein (Ikegami et al, 2007;Sirajuddin et al, 2014), or alternatively affect the microtubule binding of other proteins that affect cargo transport (Kang et al, 2008;Barlan et al, 2013;Semenova et al, 2014;Monroy et al, 2018;Tymanskyj et al, 2018). How polyglutamylation regulates the transport of distinct axonal cargoes needs to be determined.…”

Section: Of 14mentioning

confidence: 99%

Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport

et al. 2018

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Posttranslational modifications of tubulin are emerging regulators of microtubule functions. We have shown earlier that upregulated polyglutamylation is linked to rapid degeneration of Purkinje cells in mice with a mutation in the deglutamylating enzyme CCP1. How polyglutamylation leads to degeneration, whether it affects multiple neuron types, or which physiological processes it regulates in healthy neurons has remained unknown. Here, we demonstrate that excessive polyglutamylation induces neurodegeneration in a cell‐autonomous manner and can occur in many parts of the central nervous system. Degeneration of selected neurons in CCP1‐deficient mice can be fully rescued by simultaneous knockout of the counteracting polyglutamylase TTLL1. Excessive polyglutamylation reduces the efficiency of neuronal transport in cultured hippocampal neurons, suggesting that impaired cargo transport plays an important role in the observed degenerative phenotypes. We thus establish polyglutamylation as a cell‐autonomous mechanism for neurodegeneration that might be therapeutically accessible through manipulation of the enzymes that control this posttranslational modification.

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Section: Of 14mentioning

confidence: 99%

Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport

et al. 2018

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“…S2A) are largely unchanged in the presence of MAP7. MAP7 binds to kinesin-1 on the stalk domain, near the hinge region that mediates auto-inhibition (19,23,28). Thus, we asked if MAP7 acts both to recruit kinesin-1 to microtubules and relieve auto-inhibition (29,30).…”

Section: Resultsmentioning

confidence: 99%

“…To assess the possibility of an interaction between MAP7 and kinesin-2, we performed a global alignment of kinesin-1 (Heavy Chain) and kinesin-2 motors as MAP7 interacts with the stalk domain of the kinesin-1 heavy chain ( Fig. S4A) (19). We observe no homology in the kinesin-1 and kinesin-2 stalk domains, indicating that MAP7 is unlikely to directly interact with kinesin-2.…”

Section: Map7 Regulates Bidirectional Transport By Tuning the Kinesinmentioning

confidence: 99%

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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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“…For example, tau and MAP2 proteins both inhibit kinesin-1 motility (Heins et al, 1991;Seitz et al, 2002;Vershinin et al, 2007;Dixit et al, 2008). In contrast, MAP7 recruits kinesin-1 to microtubules and activates motility (Barlan et al, 2013;Tymanskyj et al, 2018;Chaudhary et al, 2019;Hooikaas et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

FRA1 modulates cortical microtubule localization of CMU proteins

Ganguly

Zhu

Chen

et al. 2019

Preprint

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Construction of the cell wall demands harmonized deposition of cellulose and matrix polysaccharides. Cortical microtubules orient the deposition of cellulose by guiding the trajectory of plasma membrane-embedded cellulose synthase complexes. Vesicles containing matrix polysaccharides are thought to be transported by the FRA1 kinesin to facilitate their secretion along cortical microtubules. The cortical microtubule cytoskeleton thus provides a platform to coordinate the delivery of cellulose and matrix polysaccharides, but the underlying molecular mechanisms remain unknown. Here, we show that the tail region of the FRA1 kinesin physically interacts with CMU proteins which are important for the microtubule-dependent guidance of cellulose synthase complexes. Interaction with CMUs did not affect microtubule binding or motility of the FRA1 kinesin but had an opposing effect on the cortical microtubule localization of CMU1 and CMU2 proteins, thus regulating the lateral stability of cortical microtubules. Phosphorylation of the FRA1 tail region by CKL6 inhibited binding to CMUs and consequently reversed the extent of cortical microtubule decoration by CMU1 and CMU2. Genetic experiments demonstrated the significance of this interaction to the growth and reproduction of Arabidopsis thaliana plants. We propose that modulation of CMU's microtubule localization by FRA1 provides a mechanism to control the coordinated deposition of cellulose and matrix polysaccharides. association of cellulose synthase and microtubules in Arabidopsis. Plant Cell 24, 163-177. S. (2013). Arabidopsis calmodulin-binding protein IQ67domain 1 localizes to microtubules and interacts with kinesin light chain-related protein-1.

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MAP7 regulates axon morphogenesis by recruiting kinesin-1 to microtubules and modulating organelle transport

Cited by 60 publications

References 57 publications

Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport

Excessive tubulin polyglutamylation causes neurodegeneration and perturbs neuronal transport

MAP7 recruits kinesin-1 to microtubules to direct organelle transport

FRA1 modulates cortical microtubule localization of CMU proteins

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