Cytoplasmic organization in cerebellar dendritic spines.

Landis, Dennis M.D.; Reese, Thomas S.

doi:10.1083/jcb.97.4.1169

Cited by 201 publications

(146 citation statements)

References 46 publications

(40 reference statements)

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“…Depending on the protocols used for specimen preparation, the synaptic cleft presents different aspects. A dense central plaque was observed in some studies; in others, fibrils running parallel to the membranes or bridging both membranes were seen (2,(8)(9)(10). In several cases, these transsynaptic fibrils seem to be regularly spaced, with a reported period ranging from 6 nm to 22 nm (11).…”

mentioning

confidence: 95%

The mammalian central nervous synaptic cleft contains a high density of periodically organized complexes

Zuber

Nikonenko

Klauser

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

206

176

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Cryo-electron microscopy of vitreous section makes it possible to observe cells and tissues at high resolution in a close-to-native state. The specimen remains hydrated; chemical fixation and staining are fully avoided. There is minimal molecular aggregation and the density observed in the image corresponds to the density in the object. Accordingly, organotypic hippocampal rat slices were vitrified under high pressure and controlled cryoprotection conditions, cryosectioned at a final thickness of Ϸ70 nm and observed below ؊170°C in a transmission electron microscope. The general aspect of the tissue compares with previous electron microscopy observations. The detailed analysis of the synapse reveals that the density of material in the synaptic cleft is high, even higher than in the cytoplasm, and that it is organized in 8.2-nm periodic transcleft complexes. Previously undescribed structures of presynaptic and postsynaptic elements are also described.Cryo-electron microscopy of vitreous section ͉ high-pressure freezing ͉ hippocampus S ynapses of the central nervous system (CNS) play a key role in neuronal information processing. Their physiology and structural organization have been extensively characterized (1, 2). The presynaptic compartment contains synaptic vesicles (SVs) filled with neurotransmitters. There is an intensive tethering and fusion activity between SVs and the presynaptic membrane. The postsynaptic membrane is covered with neurotransmitter receptors, which detect variations in neurotransmitter concentration. Postsynaptic submembrane cytoplasm is occupied by a complex network of proteins, the postsynaptic density, which modulates the strength of synaptic transmission. The space between both cells is the synaptic cleft. It contains neurotransmitter receptors and various adhesion molecules, such as N-cadherin and neural cell adhesion molecule. Their function in synapse formation and regulation is only beginning to be understood, and their precise spatial organization remains unclear (3).Resolving the molecular structure of the synapse is difficult because, on one hand, high resolution x-ray diffraction data are obtained outside their cellular context (4, 5). On the other hand, conventional electron microscopy generally fails to resolve individual proteins in their natural environment because the preparation relies on chemical fixation, dehydration, resinembedding, and heavy-metal staining and, thus, produces aggregation artifacts and artificial contrast, resulting in a limited resolution and a difficulty of interpreting the nature of the observed structures (6, 7). Freeze substitution and freeze etching, by which the specimen is immobilized by freezing and dehydrated at low temperature before being embedded in resin or replicated, were developed to reduce preparation artifacts but, even under these conditions, aggregation cannot be completely avoided. Depending on the protocols used for specimen preparation, the synaptic cleft presents different aspects. A dense central plaque was observed in some s...

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mentioning

confidence: 95%

The mammalian central nervous synaptic cleft contains a high density of periodically organized complexes

Zuber

Nikonenko

Klauser

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

206

176

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“…Quantitative immunogold electron microscopic studies have indicated that glutamate receptor subunits NR2 and GluR1 reside in regions where PSD joins the postsynaptic membrane, that PSD-95, nNOS, shank, CRIPT, and GKAP reside in the middle of the PSD and that actin, Ena/VASP, CaMKII␣, and cortactin reside in the PSD half close to the cytoplasm (39,41). Earlier EM studies have indicated that actin microfilaments may be part of the PSD structure (3,16) and that actin microfilaments are associated with the cytosolfacing surface of the PSD (76,77). These results indicate that glutamate receptors and actin along with various microfilament-associated proteins occupy respectively the peripheral regions on the exoplasm-and cytoplasm-facing sides of the PSD.…”

Section: Studying Protein-protein Interactions In the Psd By Immunoabmentioning

confidence: 99%

A Study of the Spatial Protein Organization of the Postsynaptic Density Isolated from Porcine Cerebral Cortex and Cerebellum

Yun-Hong

Chuang

Chang

et al. 2011

Molecular & Cellular Proteomics

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Postsynaptic density (PSD) is a protein supramolecule lying underneath the postsynaptic membrane of excitatory synapses and has been implicated to play important roles in synaptic structure and function in mammalian central nervous system. Here, PSDs were isolated from two distinct regions of porcine brain, cerebral cortex and cerebellum. SDS-PAGE and Western blotting analyses indicated that cerebral and cerebellar PSDs consisted of a similar set of proteins with noticeable differences in the abundance of various proteins between these samples. Subsequently, protein localization in these PSDs was analyzed by using the Nano-Depth-Tagging method. This method involved the use of three synthetic reagents, as agarose beads whose surface was covalently linked with a fluorescent, photoactivable, and cleavable chemical crosslinker by spacers of varied lengths. After its application was verified by using a synthetic complex consisting of four layers of different proteins, the Nano-Depth-Tagging method was used here to yield information concerning the depth distribution of various proteins in the PSD. The results indicated that in both cerebral and cerebellar PSDs, glutamate receptors, actin, and actin binding proteins resided in the peripheral regions within ϳ10 nm deep from the surface and that scaffold proteins, tubulin subunits, microtubule-binding proteins, and membrane cytoskeleton proteins found in mammalian erythrocytes resided in the interiors deeper than 10 nm from the surface in the PSD. Finally, by using the immunoabsorption method, binding partner proteins of two proteins residing in the interiors, PSD-95 and ␣-tubulin, and those of two proteins residing in the peripheral regions, elongation factor-1␣ and calcium, calmodulin-dependent protein kinase II ␣ subunit, of cerebral and cerebellar PSDs were identified. Overall, the results indicate a striking similarity in protein organization between the PSDs isolated from porcine cerebral cortex and cerebellum.

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“…The shape of Purkinje cell dendritic spines is regulated by the arrangement and attachment of cytoskeletal elements including actin and actin-regulating proteins such as spectrins and adducins. 109,110 Spectrin is a structural protein that forms a mesh on the cytoplasmic face of the plasma membrane and adducin binds spectrin to promote its association with filamentous actin. 111 IP6K3, but not IP6K1 or IP6K2, was shown to bind spectrin and adducin, and cells lacking IP6K3 showed reduced spectrin-adducin interaction.…”

Section: Actin Cytoskeletonmentioning

confidence: 99%

Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules

et al. 2017

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| Inositol pyrophosphates (PP-IPs) are a class of energy-rich signalling molecules found in all eukaryotic cells. These are derivatives of inositol that contain one or more diphosphate (or pyrophosphate) groups in addition to monophosphates. The more abundant and best studied PP-IPs are diphosphoinositol pentakisphosphate (IP 7 ) and bis-diphosphoinositol tetrakisphosphate (IP 8 ). These molecules can influence protein function by two mechanisms: binding and pyrophosphorylation. The former involves the specific interaction of a particular inositol pyrophosphate with a binding site on a protein, while the latter is a unique attribute of inositol pyrophosphates, wherein the β-phosphate moiety is transferred from a PP-IP to a pre-phosphorylated serine residue in a protein to generate pyrophosphoserine. Both these events can result in changes in the target protein's activity, localisation or its interaction with other partners. As a consequence of their ubiquitous presence in all eukaryotic organisms and all cell types examined till date, and their ability to modify protein function, PP-IPs have been found to participate in a wide range of metabolic, developmental, and signalling pathways.This review highlights many of the known functions of PP-IPs in the context of their temporal and spatial distribution in eukaryotic cells. The pathway of synthesis of inositol polyphosphates has been characterized in yeast, slime moulds, plants and animals. The simplest anabolic pathway, characterized in the yeast Saccharomyces cerevisiae (Fig. 1) (Fig. 1). Interestingly, the PPIP5Ks also possess a phosphatase domain which selectively cleaves the 1-position β-phosphate of 1-IP 7 and IP 8 , thus targeting the products of the kinase domain.35, 36 A recent study identified another yeast phosphatase, Siw14, that specifically targets the 5-position β-phosphate of PP-IPs 37 (Fig. 1). As PP-IPs are found in all eukaryotic organisms, they display many conserved and divergent 2, 131 Siw14, an inositol pyrophosphate phosphatase in yeast, preferentially cleaves the C5 β-phosphate on PP-IPs. 37 The yeast enzymes are depicted in purple, and mammalian enzymes are depicted in green and are bracketed. The undetermined inositol pyrophosphate structure is represented with an interrogation mark. Myoinositol contains five equatorial (parallel to the axis) and one axial (perpendicular to the axis) hydroxyl groups. Carbon atoms on the myo-inositol ring are numbered on the structures of PI(4,5)P 2 and IP 6 .

show abstract

Cytoplasmic organization in cerebellar dendritic spines.

Cited by 201 publications

References 46 publications

The mammalian central nervous synaptic cleft contains a high density of periodically organized complexes

The mammalian central nervous synaptic cleft contains a high density of periodically organized complexes

A Study of the Spatial Protein Organization of the Postsynaptic Density Isolated from Porcine Cerebral Cortex and Cerebellum

Inositol Pyrophosphates: Energetic, Omnipresent and Versatile Signalling Molecules

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