title: Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors.
abstract: The peripheral astrocyte process (PAP) preferentially associates with the synapse. The PAP, which is not found around every synapse, extends to or withdraws from it in an activity-dependent manner. Although the pre- and postsynaptic elements have been described in great molecular detail, relatively little is known about the PAP because of its difficult access for electrophysiology or light microscopy, as they are smaller than microscopic resolution. We investigated possible stimuli and mechanisms of PAP plasticity. Immunocytochemistry on rat brain sections demonstrates that the actin-binding protein ezrin and the metabotropic glutamate receptors (mGluRs) 3 and 5 are compartmentalized to the PAP but not to the GFAP-containing stem process. Further experiments applying ezrin siRNA or dominant-negative ezrin in primary astrocytes indicate that filopodia formation and motility require ezrin in the membrane/cytoskeleton bound (i.e., T567-phosphorylated) form. Glial processes around synapses in situ consistently display this ezrin form. Possible motility stimuli of perisynaptic glial processes were studied in culture, based on their similarity with filopodia. Glutamate and glutamate analogues reveal that rapid (5 min), glutamate-induced filopodia motility is mediated by mGluRs 3 and 5. Ultrastructurally, these mGluR subtypes were also localized in astrocytes in the rat hippocampus, preferentially in their fine PAPs. In vivo, changes in glutamatergic circadian activity in the hamster suprachiasmatic nucleus are accompanied by changes of ezrin immunoreactivity in the suprachiasmatic nucleus, in line with transmitter-induced perisynaptic glial motility. The data suggest that (i) ezrin is required for the structural plasticity of PAPs and (ii) mGluRs can stimulate PAP plasticity.
authors.affiliation: Institut National de la Recherche Agronomique, Unité de Nutrition et Régulation Lipidique des Fonctions Cérébrales 909, 78352 Jouy-en-Josas, France.
authors.forename: Monique
authors.initials: M
authors.lastname: Lavialle
authors.forename: Georg
authors.initials: G
authors.lastname: Aumann
authors.forename: Enrico
authors.initials: E
authors.lastname: Anlauf
authors.forename: Felicitas
authors.initials: F
authors.lastname: Pröls
authors.forename: Monique
authors.initials: M
authors.lastname: Arpin
authors.forename: Amin
authors.initials: A
authors.lastname: Derouiche
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D005260:Female; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D008647:Mesocricetus; D008856:Microscopy, Fluorescence; D016253:Microscopy, Immunoelectron; D009473:Neuronal Plasticity / Q000502:physiology; D011247:Pregnancy; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D034622:RNA Interference; D051381:Rats; D017207:Rats, Sprague-Dawley; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism / Q000502:physiology*; D000099149:Ezrin
chemical_list: D003598:Cytoskeletal Proteins; D005904:Glial Fibrillary Acidic Protein; D018698:Glutamic Acid; D049452:Green Fluorescent Proteins; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D000099149:Ezrin; C102718:metabotropic glutamate receptor 3