Structural plasticity of perisynaptic astrocyte processes involves ezrin and metabotropic glutamate receptors

Institut National de la Recherche Agronomique, Unité de Nutrition et Régulation Lipidique des Fonctions Cérébrales 909, 78352 Jouy-en-Josas, France.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 08/2011; 108(31):12915-9. DOI: 10.1073/pnas.1100957108
Source: PubMed


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.

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Available from: Amin Derouiche, Oct 06, 2015
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    • "Thus, activated Rac1 would relocalize under the plasma membrane at the extremity of astrocyte protrusions (Racchetti et al. 2012), where it has been suggested to promote the polymerization of actin filaments as well as the recruitment of ezrin, which links actin to the plasma membrane when phosphorylated at T567 (Auvinen et al. 2007). In brain slices, T567-acti- vated ezrin has been shown to be restricted to perisynaptic glial sheaths, providing a hypothetical mechanism for the stabilization of PAP remodeling after mGluRs activation (Lavialle et al. 2011). On the other hand, L-glutamate exposure in vitro has also been found to activate the small GTPase Rho, leading to suppression of astrocyte stellation via an as yet unknown mechanism involving GluTs (Chen et al. 2006). "
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    • "This led to the conclusion that astrocytic mGluR5-driven Ca 2+ signalling may be relevant only during development, but not in the adult life. An alternative explanation of these results may however relate to the polarized distribution of surface mGluR5, with a higher density on the astrocytic processes compared to their somata (Arizono et al., 2012; Lavialle et al., 2011). Based on this, it seems reasonable to postulate that this compartmentalized pattern of mGluR5 expression may account for the enhanced sensitivity of perisynaptic astrocyte processes to neural activity (Arizono et al., 2012; Panatier et al., 2011; discussed in Araque et al., 2014). "
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    • "In the confocal microscope, NDRG2 was found to be closely associated with these nerve terminal markers indicating that the protein is present in the fine distal astrocytic processes that contact nerve terminal structures including synapses (Araque et al. 1999; Haydon 2001). In contrast, GFAP that constitutes only ∼15 % of the total volume of an astrocyte is not found in the distal astrocytic processes that contact synapses (Bushong et al. 2002; Lavialle et al. 2011). "
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