Cited by 179Barrier Structure and Function StudiesRNA and protein synthesis mechanismsNeuroscience and Neuropharmacology Research

Translation in astrocyte distal processes sets molecular heterogeneity at the gliovascular interface

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Boulay, Anne- Cécile, Saubaméa, Bruno, Adam, Nicolas, Chasseigneaux, Stéphanie, Mazaré, Noémie, Gilbert, Alice, Bahin, Mathieu, Bastianelli, Leïla +10 more·2017·Cell Discovery

Abstract

Astrocytes send out long processes that are terminated by endfeet at the vascular surface and regulate vascular functions as well as homeostasis at the vascular interface. To date, the astroglial mechanisms underlying these functions have been poorly addressed. Here we demonstrate that a subset of messenger RNAs is distributed in astrocyte endfeet. We identified, among this transcriptome, a pool of messenger RNAs bound to ribosomes, the endfeetome, that primarily encodes for secreted and membrane proteins. We detected nascent protein synthesis in astrocyte endfeet. Finally, we determined the presence of smooth and rough endoplasmic reticulum and the Golgi apparatus in astrocyte perivascular processes and endfeet, suggesting for local maturation of membrane and secreted proteins. These results demonstrate for the first time that protein synthesis occurs in astrocyte perivascular distal processes that may sustain their structural and functional polarization at the vascular interface.

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References 71 · Cited by 179

Research works printed but not linked: 63

  1. Dallerac G, Chever O, Rouach N. How do astrocytes shape synaptic transmission? Insights from electrophysiology. Front Cell Neurosci 2013; 7: 159. 24101894 PMC3787198
  2. Clarke LE, Barres BA. Emerging roles of astrocytes in neural circuit development. Nat Rev Neurosci 2013; 14: 311–321. 23595014 PMC4431630
  3. Ghezali G, Dallerac G, Rouach N. Perisynaptic astroglial processes: dynamic processors of neuronal information. Brain Struct Funct 2015; 221: 2427–2442. 26026482
  4. Mathiisen TM, Lehre KP, Danbolt NC, Ottersen OP. The perivascular astroglial sheath provides a complete covering of the brain microvessels: an electron microscopic 3D reconstruction. Glia 2010; 58: 1094–1103. 20468051
  5. Abbott NJ, Patabendige AA, Dolman DE, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis 2010; 37: 13–25. 19664713
  6. Alvarez JI, Katayama T, Prat A. Glial influence on the blood brain barrier. Glia 2013; 61: 1939–1958. 24123158 PMC4068281
  7. Boulay AC, Cisternino S, Cohen-Salmon M. Immunoregulation at the gliovascular unit in the healthy brain: a focus on Connexin 43. Brain Behav Immun 2016; 56: 1–9. 26674996
  8. Verkhratsky A, Sofroniew MV, Messing A et al. Neurological diseases as primary gliopathies: a reassessment of neurocentrism. ASN Neuro 2012; 4: e00082. 22339481 PMC3320215
  9. Alvestad S, Hammer J, Hoddevik EH et al. Mislocalization of AQP4 precedes chronic seizures in the kainate model of temporal lobe epilepsy. Epilepsy Res 2013; 105: 30–41. 23357720
  10. Frydenlund DS, Bhardwaj A, Otsuka T et al. Temporary loss of perivascular aquaporin-4 in neocortex after transient middle cerebral artery occlusion in mice. Proc Natl Acad Sci USA 2006; 103: 13532–13536. 16938871 PMC1557389
  11. Yang J, Lunde LK, Nuntagij P et al. Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer's disease. J Alzheimers Dis 2011; 27: 711–722. 21891870
  12. Wolburg H, Noell S, Wolburg-Buchholz K, Mack A, Fallier-Becker P. Agrin, aquaporin-4, and astrocyte polarity as an important feature of the blood-brain barrier. Neuroscientist 2009; 15: 180–193. 19307424
  13. Kettenmann H, Verkhratsky A Neuroscience in the 21st Century. Springer Science 2016: 548–577.
  14. Buxbaum AR, Yoon YJ, Singer RH, Park HY. Single-molecule insights into mRNA dynamics in neurons. Trends Cell Biol 2015; 25: 468–475. 26052005 PMC4515374
  15. Cajigas IJ, Tushev G, Will TJ et al. The local transcriptome in the synaptic neuropil revealed by deep sequencing and high-resolution imaging. Neuron 2012; 74: 453–466. 22578497 PMC3627340
  16. Nielsen S, Nagelhus EA, Amiry-Moghaddam M et al. Specialized membrane domains for water transport in glial cells: high-resolution immunogold cytochemistry of aquaporin-4 in rat brain. J Neurosci 1997; 17: 171–180. 8987746 PMC6793699
  17. Nagelhus EA, Mathiisen TM, Ottersen OP. Aquaporin-4 in the central nervous system: cellular and subcellular distribution and coexpression with KIR4.1. Neuroscience 2004; 129: 905–913. 15561407
  18. Boulay AC, Saubamea B, Decleves X, Cohen-Salmon M. Purification of mouse brain vessels. J Vis Exp 2015; 105: e53208. PMC4692710 26574794
  19. Dieterich DC, Hodas JJ, Gouzer G et al. In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons. Nat Neurosci 2010; 13: 897–905. 20543841 PMC2920597
  20. Laird DW, Puranam KL, Revel JP. Turnover and phosphorylation dynamics of connexin43 gap junction protein in cultured cardiac myocytes. Biochem J 1991; 273: 67–72. 1846532 PMC1149880
  21. Laird DW, Castillo M, Kasprzak L. Gap junction turnover, intracellular trafficking, and phosphorylation of connexin43 in brefeldin A-treated rat mammary tumor cells. J Cell Biol 1995; 131: 1193–1203. 8522583 PMC2120642
  22. Fallon RF, Goodenough DA. Five-hour half-life of mouse liver gap-junction protein. J Cell Biol 1981; 90: 521–526. 7287816 PMC2111874
  23. De Bellis M, Pisani F, Mola MG et al. A novel human aquaporin-4 splice variant exhibits a dominant-negative activity: a new mechanism to regulate water permeability. Mol Biol Cell 2014; 25: 470–480. 24356448 PMC3923639
  24. Sheldon AL, Gonzalez MI, Krizman-Genda EN, Susarla BT, Robinson MB. Ubiquitination-mediated internalization and degradation of the astroglial glutamate transporter, GLT-1. Neurochem Int 2008; 53: 296–308. 18805448 PMC2629405
  25. Commerford SL, Carsten AL, Cronkite EP. Histone turnover within nonproliferating cells. Proc Natl Acad Sci USA 1982; 79: 1163–1165. 6951165 PMC345921
  26. Hoegg-Beiler MB, Sirisi S, Orozco IJ et al. Disrupting MLC1 and GlialCAM and ClC-2 interactions in leukodystrophy entails glial chloride channel dysfunction. Nat Commun 2014; 5: 3475. 24647135
  27. Kremer JR, Mastronarde DN, McIntosh JR. Computer visualization of three-dimensional image data using IMOD. J Struct Biol 1996; 116: 71–76. 8742726
  28. Lee S, Jha MK, Suk. K. Lipocalin-2 in the inflammatory activation of brain astrocytes. Crit Rev Immunol 2015; 35: 77–84. 26111426
  29. Zamanian JL, Xu L, Foo LC et al. Genomic analysis of reactive astrogliosis. J Neurosci 2012; 32: 6391–6410. 22553043 PMC3480225
  30. Wosik K, Cayrol R, Dodelet-Devillers A et al. Angiotensin II controls occludin function and is required for blood brain barrier maintenance: relevance to multiple sclerosis. J Neurosci 2007; 27: 9032–9042. 17715340 PMC6672193
  31. Lunde LK, Camassa LM, Hoddevik EH et al. Postnatal development of the molecular complex underlying astrocyte polarization. Brain Struct Funct 2015; 220: 2087–2101. 24777283 PMC4481305
  32. Spacek J. Ribosome-associated membrane contacts between astrocytes in the anoxic brain. Acta Neuropathol 1982; 57: 270–274. 7136505
  33. Petkovic M, Jemaiel A, Daste F et al. The SNARE Sec22b has a non-fusogenic function in plasma membrane expansion. Nat Cell Biol 2014; 16: 434–444. 24705552
  34. Krebs J, Agellon LB, Michalak M. Ca(2+) homeostasis and endoplasmic reticulum (ER) stress: an integrated view of calcium signaling. Biochem Biophys Res Commun 2015; 460: 114–121. 25998740
  35. Shigetomi E, Bushong EA, Haustein MD et al. Imaging calcium microdomains within entire astrocyte territories and endfeet with GCaMPs expressed using adeno-associated viruses. J Gen Physiol 2013; 141: 633–647. 23589582 PMC3639581
  36. Tang W, Szokol K, Jensen V et al. Stimulation-evoked Ca2+ signals in astrocytic processes at hippocampal CA3-CA1 synapses of adult mice are modulated by glutamate and ATP. J Neurosci 2015; 35: 3016–3021. 25698739 PMC4331625
  37. Otsu Y, Couchman K, Lyons DG et al. Calcium dynamics in astrocyte processes during neurovascular coupling. Nat Neurosci 2015; 18: 210–218. 25531572 PMC4651918
  38. Zorec R, Verkhratsky A, Rodriguez JJ, Parpura V. Astrocytic vesicles and gliotransmitters: slowness of vesicular release and synaptobrevin2-laden vesicle nanoarchitecture. Neuroscience 2015; 323: 67–75. 25727638
  39. Giorgi C, De Stefani D, Bononi A, Rizzuto R, Pinton P. Structural and functional link between the mitochondrial network and the endoplasmic reticulum. Int J Biochem Cell Biol 2009; 41: 1817–1827. 19389485 PMC2731816
  40. Zhou W, Chang J, Wang X et al. GM130 is required for compartmental organization of dendritic golgi outposts. Curr Biol 2014; 24: 1227–1233. 24835455 PMC4047983
  41. Pellerin L, Magistretti PJ. Neuroenergetics: calling upon astrocytes to satisfy hungry neurons. Neuroscientist 2004; 10: 53–62. 14987448
  42. Haj-Yasein NN, Jensen V, Ostby I et al. Aquaporin-4 regulates extracellular space volume dynamics during high-frequency synaptic stimulation: a gene deletion study in mouse hippocampus. Glia 2012; 60: 867–874. 22419561
  43. MacVicar BA, Newman EA. Astrocyte regulation of blood flow in the brain. Cold Spring Harb Perspect Biol 2015; 7. PMC4448617 25818565
  44. Sahlender DA, Savtchouk I, Volterra A. What do we know about gliotransmitter release from astrocytes? Philos Trans R Soc Lond B Biol Sci 2014; 369: 20130592. 25225086 PMC4173278
  45. Wang X, Chun SJ, Treloar H et al. Localization of Nogo-A and Nogo-66 receptor proteins at sites of axon-myelin and synaptic contact. J Neurosci 2002; 22: 5505–5515. 12097502 PMC6758202
  46. Lee H, Raiker SJ, Venkatesh K et al. Synaptic function for the Nogo-66 receptor NgR1: regulation of dendritic spine morphology and activity-dependent synaptic strength. J Neurosci 2008; 28: 2753–2765. 18337405 PMC6670664
  47. Mohebiany AN, Nikolaienko RM, Bouyain S, Harroch S. Receptor-type tyrosine phosphatase ligands: looking for the needle in the haystack. FEBS J 2013; 280: 388–400. 22682003 PMC3753797
  48. Schnepp A, Komp Lindgren P, Hulsmann H et al. Mouse testican-2. Expression, glycosylation, and effects on neurite outgrowth. J Biol Chem 2005; 280: 11274–11280. 15657052
  49. Robinson MB, Jackson JG. Astroglial glutamate transporters coordinate excitatory signaling and brain energetics. Neurochem Int 2016; 98: 56–71. 27013346 PMC4969184
  50. Sibille J, Pannasch U, Rouach N. Astroglial potassium clearance contributes to short-term plasticity of synaptically evoked currents at the tripartite synapse. J Physiol 2014; 592: 87–102. 24081156 PMC3903353
  51. Kao DI, Aldridge GM, Weiler IJ, Greenough WT. Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein. Proc Natl Acad Sci USA 2010; 107: 15601–15606. 20713728 PMC2932564
  52. Fallini C, Bassell GJ, Rossoll W. The ALS disease protein TDP-43 is actively transported in motor neuron axons and regulates axon outgrowth. Hum Mol Genet 2012; 21: 3703–3718. 22641816 PMC3406762
  53. Alami NH, Smith RB, Carrasco MA et al. Axonal transport of TDP-43 mRNA granules is impaired by ALS-causing mutations. Neuron 2014; 81: 536–543. 24507191 PMC3939050
  54. Jablonka S, Bandilla M, Wiese S et al. Co-regulation of survival of motor neuron (SMN) protein and its interactor SIP1 during development and in spinal muscular atrophy. Hum Mol Genet 2001; 10: 497–505. 11181573
  55. Zhang HL, Pan F, Hong D et al. Active transport of the survival motor neuron protein and the role of exon-7 in cytoplasmic localization. J Neurosci 2003; 23: 6627–6637. 12878704 PMC6740639
  56. de la Grange P, Gratadou L, Delord M, Dutertre M, Auboeuf D. Splicing factor and exon profiling across human tissues. Nucleic Acids Res 2010; 38: 2825–2838. 20110256 PMC2875023
  57. Nikitin A, Egorov S, Daraselia N, Mazo I. Pathway studio--the analysis and navigation of molecular networks. Bioinformatics 2003; 19: 2155–2157. 14594725
  58. Jourdren L, Bernard M, Dillies MA, Le Crom S. Eoulsan: a cloud computing-based framework facilitating high throughput sequencing analyses. Bioinformatics 2012; 28: 1542–1543. 22492314
  59. Langmead B, Trapnell C, Pop M, Salzberg SL. Ultrafast and memory-efficient alignment of short DNA sequences to the human genome. Genome Biol 2009; 10: R25. 19261174 PMC2690996
  60. Li H, Handsaker B, Wysoker A et al. The sequence alignment/map format and SAMtools. Bioinformatics 2009; 25: 2078–2079. 19505943 PMC2723002
  61. Anders S, Pyl PT, Huber W. HTSeq--a Python framework to work with high-throughput sequencing data. Bioinformatics 2015; 31: 166–169. 25260700 PMC4287950
  62. Love MI, Huber W, Anders S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 2014; 15: 550. 25516281 PMC4302049
  63. Ezan P, Andre P, Cisternino S et al. Deletion of astroglial connexins weakens the blood-brain barrier. J Cereb Blood Flow Metab 2012; 32: 1457–1467. 22472609 PMC3421093

Authors
Boulay, A. C., Saubaméa, B., Adam, N., Chasseigneaux, S., Mazaré, N., Gilbert, A., Bahin, M., Bastianelli, L., Blugeon, C., Perrin, S., Pouch, J., Ducos, B., Le Crom, S., Genovesio, A., Chrétien, F., Declèves, X., Laplanche, J.-L., & Cohen-Salmon, M.
Affiliations
  • Centre National de la Recherche Scientifique (FR)
  • Inserm (FR)
  • École Normale Supérieure - PSL (FR)
  • Institut Pasteur (FR)
Venue
Cell Discovery
Published
2017-03-28
Volume
3
Issue
1
Pages
17005-17005
ISSN
2056-5968 (ISSN-L)
OpenAlex
W2597423760
Cited by
179
References
71
Citations by year
2026: 20 · 2025: 17 · 2024: 14 · 2023: 31 · 2022: 23 · 2021: 23 · 2020: 20 · 2019: 19 · 2018: 8 · 2017: 4
FWCI
6.96
Type
journal article
Language
en
Open access
Locations
  • Cell Discovery (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion)
  • HAL (submittedVersion, cc-by)
Funders
  • Agence Nationale de la Recherche (ANR-10-INBS-0009)
  • Fondation pour la Recherche Médicale
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
astrocytes, astrocyte endfeet, mRNA localization, nascent protein synthesis, ribosome-bound mRNA, secreted proteins, membrane proteins, endoplasmic reticulum, Golgi apparatus, astrocyte polarization, astrocyte transcriptome

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