Coordination between Transport and Local Translation in Neurons

[en] The axonal microtubules (MTs) support long-distance transport of cargoes that are dispatched to distinct cellular subcompartments. Among them, mRNAs are directly transported in membraneless ribonucleoprotein (RNP) granules that, together with ribosomes, can also hitchhike on fast-moving membrane-bound organelles for accurate transport along MTs. These organelles serve as platforms for mRNA translation, thus generating axonal foci of newly synthesized proteins. Local translation along axons not only supports MT network integrity but also modulates the processivity and function of molecular motors to allow proper traf- ficking of cargoes along MTs. Thus, identifying the mechanisms that coordinate axonal transport with local protein synthesis will shed new light on the processes underlying axon development and maintenance, whose deregulation often contribute to neurological disorders.

Disciplines :

Biochemistry, biophysics & molecular biology

Author, co-author :

Broix, Loïc ^✱; Université de Liège - ULiège > GIGA Stem Cells - Molecular Regulation of Neurogenesis

Turchetto, Silvia ^✱; Université de Liège - ULiège > GIGA Stem Cells - Molecular Regulation of Neurogenesis

Nguyen, Laurent ; Université de Liège - ULiège > GIGA Stem Cells - Molecular Regulation of Neurogenesis

^✱ These authors have contributed equally to this work.

Language :

English

Title :

Coordination between Transport and Local Translation in Neurons

Publication date :

2021

Journal title :

Trends in Cell Biology

ISSN :

0962-8924

eISSN :

1879-3088

Publisher :

Elsevier, Netherlands

Peer reviewed :

Peer Reviewed verified by ORBi

Available on ORBi :

since 16 February 2021

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2 (2 by ULiège)

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Bibliography

Ries, R.J., et al. m6A enhances the phase separation potential of mRNA. Nature 571 (2019), 424–428.
Anderson, P., Kedersha, N., RNA granules. J. Cell Biol. 172 (2006), 803–808.
Czaplinski, K., Understanding mRNA trafficking: are we there yet?. Semin. Cell Dev. Biol. 32 (2014), 63–70.
El Fatimy, R., et al. Tracking the fragile X mental retardation protein in a highly ordered neuronal ribonucleoparticles population: a link between stalled polyribosomes and RNA granules. PLoS Genet., 12, 2016, e1006192.
Elvira, G., et al. Characterization of an RNA granule from developing brain. Mol. Cell. Proteomics 5 (2006), 635–651.
Kanai, Y., et al. Kinesin transports RNA: isolation and characterization of an RNA-transporting granule. Neuron 43 (2004), 513–525.
Baumann, S., et al. A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs. Sci. Adv., 6, 2020, eaaz1588.
Wu, H., et al. A kinesin adapter directly mediates dendritic mRNA localization during neural development in mice. J. Biol. Chem. 295 (2020), 6605–6628.
Hendricks, A.G., et al. Motor coordination via a tug-of-war mechanism drives bidirectional vesicle transport. Curr. Biol. 20 (2010), 697–702.
Gumy, L.F., et al. MAP2 defines a pre-axonal filtering zone to regulate KIF1- versus KIF5-dependent cargo transport in sensory neurons. Neuron 94 (2017), 347–362.e7.
Messitt, T.J., et al. Multiple kinesin motors coordinate cytoplasmic RNA transport on a subpopulation of microtubules in Xenopus oocytes. Dev. Cell 15 (2008), 426–436.
Pasciuto, E., Bagni, C., SnapShot: FMRP mRNA targets and diseases. Cell 158 (2014), 1446–1446.e1.
Batish, M., et al. Neuronal mRNAs travel singly into dendrites. Proc. Natl. Acad. Sci. U. S. A. 109 (2012), 4645–4650.
Turner-Bridger, B., et al. Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons. Proc. Natl. Acad. Sci. U. S. A. 115 (2018), E9697–E9706.
Hammer, J.A., Sellers, J.R., Walking to work: roles for class v myosins as cargo transporters. Nat. Rev. Mol. Cell Biol. 13 (2012), 13–26.
Ohashi, S., et al. Identification of mRNA/protein (mRNP) complexes containing Purα, mStaufen, fragile X protein, and myosin Va and their association with rough endoplasmic reticulum equipped with a kinesin motor. J. Biol. Chem. 277 (2002), 37804–37810.
Yoshimura, A., et al. Myosin-Va facilitates the accumulation of mRNA/protein complex in dendritic spines. Curr. Biol. 16 (2006), 2345–2351.
Mitsumori, K., et al. Components of RNA granules affect their localization and dynamics in neuronal dendrites. Mol. Biol. Cell 28 (2017), 1412–1417.
Lindsay, A.J., et al. Identification and characterization of multiple novel Rab-myosin Va interactions. Mol. Biol. Cell 24 (2013), 3420–3434.
Balasanyan, V., Arnold, D.B., Actin and myosin-dependent localization of mRNA to dendrites. PLoS One, 9, 2014, e92349.
Pathak, D., et al. Evidence that myosin activity opposes microtubule-based axonal transport of mitochondria. J. Neurosci. 30 (2010), 8984–8992.
Nalavadi, V.C., et al. Regulation of zipcode binding protein 1 transport dynamics in axons by myosin va. J. Neurosci. 32 (2012), 15133–15141.
Bommel, B., et al. F-actin patches associated with glutamatergic synapses control positioning of dendritic lysosomes. EMBO J. 38 (2019), 1–17.
Tushev, G., et al. Alternative 3′ UTRs modify the localization, regulatory potential, stability, and plasticity of mRNAs in neuronal compartments. Neuron 98 (2018), 495–511.e6.
Nagano, S., et al. TDP-43 transports ribosomal protein mRNA to regulate axonal local translation in neuronal axons. Acta Neuropathol. 140 (2020), 695–713.
Merianda, T.T., et al. Axonal localization of neuritin/CPG15 mRNA in neuronal populations through distinct 5′ and 3′ UTR elements. J. Neurosci. 33 (2013), 13735–13742.
Martínez, J.C., et al. Pum2 shapes the transcriptome in developing axons through retention of target mRNAs in the cell body. Neuron 104 (2019), 931–946.e5.
Fritzsche, R., et al. Interactome of two diverse RNA granules links mRNA localization to translational repression in neurons. Cell Rep. 5 (2013), 1749–1762.
Graber, T.E., et al. UPF1 governs synaptic plasticity through association with a STAU2 RNA granule. J. Neurosci. 37 (2017), 9116–9131.
Graber, T.E., et al. Reactivation of stalled polyribosomes in synaptic plasticity. Proc. Natl. Acad. Sci. U. S. A. 110 (2013), 16205–16210.
Langille, J.J., et al. Polysomes identified by live imaging of nascent peptides are stalled in hippocampal and cortical neurites. Learn. Mem. 26 (2019), 351–362.
Wells, D.G., RNA-binding proteins: a lesson in repression. J. Neurosci. 26 (2006), 7135–7138.
Na, Y., et al. Real-time imaging reveals properties of glutamate-induced Arc/Arg 3.1 translation in neuronal dendrites. Neuron 91 (2016), 561–573.
Gopal, P.P., et al. Amyotrophic lateral sclerosis-linked mutations increase the viscosity of liquid-like TDP-43 RNP granules in neurons. Proc. Natl. Acad. Sci. U. S. A. 114 (2017), E2466–E2475.
Shiina, N., Liquid- and solid-like RNA granules form through specific scaffold proteins and combine into biphasic granules. J. Biol. Chem. 294 (2019), 3532–3548.
Yasuda, K., et al. The RNA-binding protein Fus directs translation of localized mRNAs in APC-RNP granules. J. Cell Biol. 203 (2013), 737–746.
Mateju, D., et al. Single-molecule imaging reveals translation of mRNAs localized to stress granules. Cell 183 (2020), 1801–1812.
Wu, B., et al. Translation dynamics of single mRNAs in live cells and neurons. Science 352 (2016), 1430–1435.
Wang, C., et al. Real-time imaging of translation on single mRNA transcripts in live cells. Cell 165 (2016), 990–1001.
Guedes-Dias, P., Holzbaur, E.L.F., Axonal transport: driving synaptic function. Science, 366, 2019, eaaw9997.
Farías, G.G., et al. BORC/kinesin-1 ensemble drives polarized transport of lysosomes into the axon. Proc. Natl. Acad. Sci. U. S. A. 114 (2017), E2955–E2964.
van Spronsen, M., et al. TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites. Neuron 77 (2013), 485–502.
De Pace, R., et al. Synaptic vesicle precursors and lysosomes are transported by different mechanisms in the axon of mammalian neurons. Cell Rep., 31, 2020, 107775.
Salogiannis, J., Reck-Peterson, S.L., Hitchhiking: a non-canonical mode of microtubule-based transport. Trends Cell Biol. 27 (2017), 141–150.
Higuchi, Y., et al. Early endosome motility spatially organizes polysome distribution. J. Cell Biol. 204 (2014), 343–357.
Baumann, S., et al. Endosomal transport of septin mRNA and protein indicates local translation on endosomes and is required for correct septin filamentation. EMBO Rep. 15 (2014), 94–102.
Olgeiser, L., et al. The key protein of endosomal mRNP transport Rrm4 binds translational landmark sites of cargo mRNAs. EMBO Rep. 20 (2019), 1–17.
Liao, Y.-C., et al. RNA granules hitchhike on lysosomes for long-distance transport, using annexin A11 as a molecular tether. Cell 179 (2019), 147–164.e20.
Cioni, J.-M., et al. Late endosomes act as mRNA translation platforms and sustain mitochondria in axons article late endosomes act as mRNA translation platforms and sustain mitochondria in axons. Cell 176 (2019), 56–72.e15.
Corradi, E., et al. Axonal precursor mi RNA s hitchhike on endosomes and locally regulate the development of neural circuits. EMBO J. 39 (2020), 1–24.
Yoon, B.C., et al. Local translation of extranuclear lamin B promotes axon maintenance. Cell 148 (2012), 752–764.
Béthune, J., et al. Membrane-associated RNA-binding proteins orchestrate organelle-coupled translation. Trends Cell Biol. 29 (2019), 178–188.
Carter, S.D., et al. Ribosome-associated vesicles: a dynamic subcompartment of the endoplasmic reticulum in secretory cells. Sci. Adv., 6, 2020, eaay9572.
Hinckelmann, et al. Self-propelling vesicles define glycolysis as the minimal energy machinery for neuronal transport. Nat. Publ. Gr., 7, 2016, 13233.
Zala, D., et al. Vesicular glycolysis provides on-board energy for fast axonal transport. Cell 152 (2013), 479–491.
Even, A., et al. ATAT1-enriched vesicles promote microtubule acetylation via axonal transport. Sci. Adv., 5, 2019, eaax2705.
Bisbal, M., et al. KIF4 mediates anterograde translocation and positioning of ribosomal constituents to axons. J. Biol. Chem. 284 (2009), 9489–9497.
Noma, K., et al. Microtubule-dependent ribosome localization in C. elegans neurons. Elife 6 (2017), 1–23.
Biever, A., et al. Monosomes actively translate synaptic mRNAs in neuronal processes. Science, 367, 2020, eaay4991.
Shigeoka, T., et al. Dynamic axonal translation in developing and mature visual circuits. Cell 166 (2016), 181–192.
Shigeoka, T., et al. On-site ribosome remodeling by locally synthesized ribosomal proteins in axons. Cell Rep. 29 (2019), 3605–3619.e10.
Twelvetrees, A.E., The lifecycle of the neuronal microtubule transport machinery. Semin. Cell Dev. Biol., 107, 2020, 7481.
Hafner, A.S., et al. Local protein synthesis is a ubiquitous feature of neuronal pre- And postsynaptic compartments. Science, 364, 2019, eaau3644.
Maciel, R., et al. The human motor neuron axonal transcriptome is enriched for transcripts related to mitochondrial function and microtubule-based axonal transport. Exp. Neurol. 307 (2018), 155–163.
Villarin, J.M., et al. Local synthesis of dynein cofactors matches retrograde transport to acutely changing demands. Nat. Commun., 7, 2016, 13865.
Walker, C.A., et al. Aβ 1–42 triggers the generation of a retrograde signaling complex from sentinel mRNA s in axons. EMBO Rep. 19 (2018), 1–13.
Perlson, E., et al. Vimentin-dependent spatial translocation of an activated MAP kinase in injured nerve. Neuron 45 (2005), 715–726.
Sun, F., et al. Sunday Driver/JIP3 binds kinesin heavy chain directly and enhances its motility. EMBO J. 30 (2011), 3416–3429.
Blasius, T.L., et al. Two binding partners cooperate to activate the molecular motor Kinesin-1. J. Cell Biol. 176 (2007), 11–17.
Niwa, S., et al. KIF1Bβ- and KIF1A-mediated axonal transport of presynaptic regulator Rab3 occurs in a GTP-dependent manner through DENN/MADD. Nat. Cell Biol. 10 (2008), 1269–1279.
Ma, B., et al. Huntingtin mediates dendritic transport of β-actin mRNA in rat neurons. Sci. Rep. 1 (2011), 1–11.
Savas, J.N., et al. A role for Huntington disease protein in dendritic RNA granules. J. Biol. Chem. 285 (2010), 13142–13153.
Fu, M. meng, Holzbaur, E.L.F., Integrated regulation of motor-driven organelle transport by scaffolding proteins. Trends Cell Biol. 24 (2014), 564–574.
Roy, S., Seeing the unseen: the hidden world of slow axonal transport. Neuroscience 20 (2014), 71–81.
Chuang, C.F., et al. Unbiased proteomic study of the axons of cultured rat cortical neurons. J. Proteome Res. 17 (2018), 1953–1966.
Poulopoulos, A., et al. Subcellular transcriptomes and proteomes of developing axon projections in the cerebral cortex. Nature, 565, 2019, 365-360.
Preitner, N., et al. APC is an RNA-binding protein, and its interactome provides a link to neural development and microtubule assembly. Cell 158 (2014), 368–382.
Triclin, S., et al. Self-repair protects microtubules from their destruction by molecular motors. bioRxiv, 2018 Published online December 17, 2018. https://doi.org/10.1101/499020.
Dumont, E.L.P., et al. Molecular wear of microtubules propelled by surface-adhered kinesins. Nat. Nanotechnol. 10 (2015), 166–169.
Femino, A.M., et al. Visualization of single RNA transcripts in situ. Science 280 (1998), 585–590.
Raj, A., et al. Imaging individual mRNA molecules using multiple singly labeled probes. Nat. Methods 5 (2008), 877–879.
Tsanov, N., et al. smiFISH and FISH-quant-a flexible single RNA detection approach with super-resolution capability. Nucleic Acids Res., 44, 2016, 165.
Sinnamon, J.R., Czaplinski, K., RNA detection in situ with FISH-STICs. RNA 20 (2014), 260–266.
Wang, F., et al. RNAscope: A novel in situ RNA analysis platform for formalin-fixed, paraffin-embedded tissues. J. Mol. Diagnostics 14 (2012), 22–29.
Chen, K.H., et al. Spatially resolved, highly multiplexed RNA profiling in single cells. Science, 348, 2015, aaa6090-aaa6090.
Tyagi, S., Kramer, F.R., Molecular beacons: probes that fluoresce upon hybridization. Nat. Biotechnol. 14 (1996), 303–308.
Tyagi, S., et al. Multicolor molecular beacons for allele discrimination. Nat. Biotechnol. 16 (1998), 49–53.
Paige, J.S., et al. RNA mimics of green fluorescent protein. Science 333 (2011), 642–646.
Filonov, G.S., et al. Broccoli: rapid selection of an RNA mimic of green fluorescent protein by fluorescence-based selection and directed evolution. J. Am. Chem. Soc. 136 (2014), 16299–16308.
Dolgosheina, E.V., et al. RNA Mango aptamer-fluorophore: a bright, high-affinity complex for RNA labeling and tracking. ACS Chem. Biol. 9 (2014), 2412–2420.
Chen, X., et al. Visualizing RNA dynamics in live cells with bright and stable fluorescent RNAs. Nat. Biotechnol. 37 (2019), 1287–1293.
Buxbaum, A.R., et al. In the right place at the right time: visualizing and understanding mRNA localization. Nat. Rev. Mol. Cell Biol. 16 (2015), 95–109.
Chao, J.A., et al. Structural basis for the coevolution of a viral RNA-protein complex. Nat. Struct. Mol. Biol. 15 (2008), 103–105.
Yoshimura, H., Live cell imaging of endogenous RNAs using Pumilio homology domain mutants: principles and applications. Biochemistry 57 (2018), 200–208.
Halstead, J.M., et al. TRICK: A Single-Molecule Method for Imaging the First Round of Translation in Living Cells and Animals. 2016, Elsevier.
Ruijtenberg, S., et al. RNA Detection. 2018, Springer New York.
Yan, X., et al. Dynamics of translation of single mRNA molecules in vivo resource dynamics of translation of single mRNA molecules in vivo. Cell 165 (2016), 976–989.
Boersma, S., et al. Multi-color single-molecule imaging uncovers extensive heterogeneity in mRNA decoding. Cell 178 (2019), 458–472.e19.
Morisaki, T., et al. Real-time quantification of single RNA translation dynamics in living cells. Science 352 (2016), 1425–1429.
Zhao, N., et al. A genetically encoded probe for imaging nascent and mature HA-tagged proteins in vivo. Nat. Commun., 10, 2019, 2947.
Buhr, F., et al. Design of photocaged puromycin for nascent polypeptide release and spatiotemporal monitoring of translation. Angew. Chem. Int. Ed. 54 (2015), 3717–3721.
Tom Dieck, S., et al. Direct visualization of newly synthesized target proteins in situ. Nat. Methods 12 (2015), 411–414.
Bastide, A., et al. The RiboPuromycylation Method (RPM): an immunofluorescence technique to map translation sites at the sub-cellular level. Bio-Protocol 8 (2018), 1–20.
Hobson, B.D., et al. Elongation inhibitors do not prevent the release of puromycylated nascent polypeptide chains from ribosomes. Elife 9 (2020), 1–47.
Enam, S.U., et al. Puromycin reactivity does not accurately localize translation at the subcellular level. Elife 9 (2020), 1–34.
Dieterich, D.C., et al. In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons. Nat. Neurosci. 13 (2010), 897–905.
Guo, W., et al. Axonal transport defects and neurodegeneration: molecular mechanisms and therapeutic implications. Semin. Cell Dev. Biol. 99 (2020), 133–150.
Millecamps, S., Julien, J.-P., Axonal transport deficits and neurodegenerative diseases. Nat. Rev. Neurosci. 14 (2013), 161–176.
Thelen, M.P., Kye, M.J., The role of RNA binding proteins for local mRNA translation: implications in neurological disorders. Front. Mol. Biosci. 6 (2020), 1–13.
Alami, N.H., et al. Axonal transport of TDP-43 mRNA granules in neurons is impaired by ALS-causing mutations. Neuron 81 (2014), 536–543.
Donlin-Asp, P.G., et al. A role for the survival of motor neuron protein in mRNP assembly and transport. Curr. Opin. Neurobiol. 39 (2016), 53–61.