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.A strocytes act as a third partner in synaptic signal processing by responding to neurotransmitters and by releasing "gliotransmitters" (1, 2). Structurally, the astrocyte functions mainly through its peripheral processes, which constitute approximately 80% of the cell's membrane (3). These peripheral astrocyte processes (PAPs) are frequently extremely fine (<50 nm) and display an extreme surface-to-volume ratio. They are rarely studied in live tissue, as they are not directly accessible to electrophysiology, cannot be isolated for biochemistry, and are smaller than microscopic resolution. However, they also wrap synapses, but most studies on glia-synaptic interaction can only indiscriminately refer to them as the astrocyte. At the ultrastructural level, the PAPs, although abundant in the neuropil, specifically prefer contacting synapses and dendrites versus axons (4). The synaptic wrapping is highly dynamic (5-9) and also activity-dependent even in the context of physiological functions, such as motor learning, daily fluctuations of the circadian clock, lactation, parturition, or dehydration (10-15). Here, we asked two questions about the structural basis of glia-synaptic interaction: What is the stimulus for PAP plasticity, and what are the intra...

These results show that in human, rat, and mouse glomeruli, alpha8 integrin is strongly and exclusively expressed in MCs. Gene expression of alpha8 is regulated in cultured MCs, and alpha8 protein abundance is regulated in vivo and in MC culture. It is currently unclear what functional properties this integrin receptor protein has with regard to MC anchorage to extracellular matrix and modulation of the MC phenotype in normal and diseased glomeruli. However, in view of its abundance in the mesangium, alpha8beta1 integrin could be an important MC receptor of matrix ligands and may play a role in the embryology, physiology, and pathophysiology of the glomerular capillary tuft.

Long-range intercellular communication is essential for the regulation of embryonic development. Apart from simple diffusion, various modes of signal transfer have been described in the literature. Here, we describe a novel type of cellular extensions found in epithelial cells of the somites in chicken embryos. These filopodia-like protrusions span the subectodermal space overlying the dorsal surface of the somites and contact the ectoderm. We show that these protrusions are actin-and tubulin-positive and require Rac1 for their formation. The presence of glycophosphatidylinositol-anchored proteins and net retrograde trafficking of the transmembrane Wnt-receptor Frizzled-7 along the protrusions indicate their role in signal transport and distribution. Taken together, our data suggest a role of filopodia-like protrusions in mediating signaling events between distant epithelial cells during embryonic development.

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