Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors.
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Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors. / Lavialle, Monique; Aumann, Georg; Anlauf, Enrico; Pröls, Felicitas; Arpin, Monique; Derouiche, Amin.
in: P NATL ACAD SCI USA, Jahrgang 108, Nr. 31, 31, 2011, S. 12915-12919.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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T1 - Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors.
AU - Lavialle, Monique
AU - Aumann, Georg
AU - Anlauf, Enrico
AU - Pröls, Felicitas
AU - Arpin, Monique
AU - Derouiche, Amin
PY - 2011
Y1 - 2011
N2 - 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.
AB - 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.
KW - Animals
KW - Male
KW - Female
KW - Immunohistochemistry
KW - Cells, Cultured
KW - Cricetinae
KW - Rats
KW - Rats, Sprague-Dawley
KW - Microscopy, Fluorescence
KW - Pregnancy
KW - RNA Interference
KW - Glial Fibrillary Acidic Protein/metabolism
KW - Green Fluorescent Proteins/genetics/metabolism
KW - Neuronal Plasticity/physiology
KW - Microscopy, Immunoelectron
KW - Hippocampus/cytology/metabolism
KW - Astrocytes/cytology/metabolism/ultrastructure
KW - Cytoskeletal Proteins/genetics/metabolism
KW - Glutamic Acid/pharmacology
KW - Mesocricetus
KW - Pseudopodia/drug effects/metabolism/physiology
KW - Receptors, Metabotropic Glutamate/metabolism
KW - Synapses/metabolism/physiology
KW - Animals
KW - Male
KW - Female
KW - Immunohistochemistry
KW - Cells, Cultured
KW - Cricetinae
KW - Rats
KW - Rats, Sprague-Dawley
KW - Microscopy, Fluorescence
KW - Pregnancy
KW - RNA Interference
KW - Glial Fibrillary Acidic Protein/metabolism
KW - Green Fluorescent Proteins/genetics/metabolism
KW - Neuronal Plasticity/physiology
KW - Microscopy, Immunoelectron
KW - Hippocampus/cytology/metabolism
KW - Astrocytes/cytology/metabolism/ultrastructure
KW - Cytoskeletal Proteins/genetics/metabolism
KW - Glutamic Acid/pharmacology
KW - Mesocricetus
KW - Pseudopodia/drug effects/metabolism/physiology
KW - Receptors, Metabotropic Glutamate/metabolism
KW - Synapses/metabolism/physiology
M3 - SCORING: Journal article
VL - 108
SP - 12915
EP - 12919
JO - P NATL ACAD SCI USA
JF - P NATL ACAD SCI USA
SN - 0027-8424
IS - 31
M1 - 31
ER -
