Well-aligned macroscopic fibers composed solely of single-walled carbon nanotubes (SWNTs) were produced by conventional spinning. Fuming sulfuric acid charges SWNTs and promotes their ordering into an aligned phase of individual mobile SWNTs surrounded by acid anions. This ordered dispersion was extruded via solution spinning into continuous lengths of macroscopic neat SWNT fibers. Such fibers possess interesting structural composition and physical properties.

In excitatory synapses of the brain, specific receptors in the postsynaptic membrane lie ready to respond to the release of the neurotransmitter glutamate from the presynaptic terminal. Upon stimulation, these glutamate receptors activate multiple biochemical pathways that transduce signals into the postsynaptic neuron. Different kinds of synaptic activity elicit different patterns of postsynaptic signals that lead to short- or long-lasting strengthening or weakening of synaptic transmission. The complex molecular mechanisms that underlie postsynaptic signaling and plasticity are beginning to emerge.

NMDA receptors (NMDARs) control bidirectional synaptic plasticity by regulating postsynaptic AMPA receptors (AMPARs). Here we show that NMDAR activation can have differential effects on AMPAR trafficking, depending on the subunit composition of NMDARs. In mature cultured neurons, NR2A-NMDARs promote, whereas NR2B-NMDARs inhibit, the surface expression of GluR1, primarily by regulating its surface insertion. In mature neurons, NR2B is coupled to inhibition rather than activation of the Ras-ERK pathway, which drives surface delivery of GluR1. Moreover, the synaptic Ras GTPase activating protein (GAP) SynGAP is selectively associated with NR2B-NMDARs in brain and is required for inhibition of NMDAR-dependent ERK activation. Preferential coupling of NR2B to SynGAP could explain the subtype-specific function of NR2B-NMDARs in inhibition of Ras-ERK, removal of synaptic AMPARs, and weakening of synaptic transmission.

The postsynaptic density (PSD) of central excitatory synapses plays a key role in postsynaptic signal transduction and contains a high concentration of glutamate receptors and associated scaffold and signaling proteins. We report here a comprehensive analysis of purified PSD fractions by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). We identified 374 different proteins that copurified with the PSD structure and discovered thirteen phosphorylated sites from eight proteins. These proteins were classified into numerous functional groups, implying that the signaling pathways in the PSD are complex and diverse. Furthermore, using quantitative mass spectrometry, we measured the molar concentration and relative stoichiometries of a number of glutamate receptor subunits and scaffold proteins in the postsynaptic density. Thus this proteomic study reveals crucial information about molecular abundance as well as molecular diversity in the PSD, and provides a basis for further studies on the molecular mechanisms of synaptic function and plasticity.In excitatory synapses of the brain, the postsynaptic density (PSD) 1 is a microdomain of the postsynaptic membrane specialized for signaling and plasticity (1-3). It contains neurotransmitter receptors (particularly for the transmitter glutamate), receptor-associated scaffold proteins, cytoskeletal elements, and regulatory enzymes, which are assembled together in a disk-like structure, ϳ30 -40-nm thick and a few hundred nanometers wide (4). Glutamate receptors in the PSD are organized into supramolecular signaling complexes by interacting with specific PDZ (PSD-95, Dlg, ZO-1 homology) domain-containing scaffolds (such as PSD-95/SAP90) and their associated proteins.The molecular architecture of the PSD is specialized for signal transduction, but it is also highly modifiable to allow for strengthening and weakening of synaptic transmission (1-3). The function and composition of the PSD is dynamically regulated in response to neural activity, involving mechanisms such as protein phosphorylation (3), local translation (5), ubiquitination and degradation (6, 7), and subcellular redistribution (8). Because of the central role of the PSD in synaptic transmission and plasticity, a comprehensive knowledge of the protein composition of the PSD will be extremely useful for understanding synaptic mechanisms, even if this composition represents only an averaged "snapshot" of a heterogeneous population of changing PSDs.Over years, protein components of the PSD have been gradually discovered by biochemical and yeast two-hybrid approaches. The PSD is typically purified through differential centrifugation, sucrose gradient sedimentation and detergent extraction, because the PSD structure cannot be solubilized with mild nonionic detergents such as Triton X-100 (4). Kennedy and co-workers (9, 10) discovered several PSD proteins (e.g. PSD-95, densin-180) by sequencing of protein bands from one-dimensional gels of PSD preparations. Walsh and Kuruc (11) employed two-dimensi...

The structure and function of presynaptic and postsynaptic components of the synapse are highly coordinated. How such coordination is achieved and the molecules involved in this process have not been clarified. Several lines of evidence suggest that presynaptic functionalities are regulated by retrograde mechanisms from the postsynaptic side. We therefore sought postsynaptic mechanisms responsible for trans-synaptic regulation of presynaptic function at excitatory synapses in rat hippocampal CA1 pyramidal neurons. We show here that the postsynaptic complex of scaffolding protein PSD-95 and neuroligin can modulate the release probability of transmitter vesicles at synapse in a retrograde way, resulting in altered presynaptic short-term plasticity. Presynaptic beta-neurexin serves as a likely presynaptic mediator of this effect. Our results indicate that trans-synaptic protein-protein interactions can link postsynaptic and presynaptic function.

Parkinson’s disease is the second most common neurodegenerative disorder without effective treatment. It is generally sporadic with unknown etiology. However, genetic studies of rare familial forms have led to the identification of mutations in several genes, which are linked to typical Parkinson’s disease or parkinsonian disorders. The pathogenesis of Parkinson’s disease remain largely elusive. Here, we report a novel genetic locus for an autosomal dominant, clinically typical and Lewy body confirmed Parkinson’s disease on the short arm of chromosome 20 (20pter-p12) and TMEM230 as the disease-causing gene. We show that TMEM230 encodes a transmembrane protein of secretory/recycling vesicles, including synaptic vesicles in neurons. The disease-linked TMEM230 mutants impair synaptic vesicle trafficking. Our data provide the first genetic evidence that a mutant transmembrane protein of synaptic vesicles in neurons is etiologically linked to Parkinson’s disease, with novel implications in understanding the pathogenic mechanism of Parkinson’s disease and for developing rational therapies.

The scaffold protein PSD-95 promotes the maturation and strengthening of excitatory synapses, functions that require proper localization of PSD-95 in the postsynaptic density (PSD). Here we report that phosphorylation of ser-295 enhances the synaptic accumulation of PSD-95 and the ability of PSD-95 to recruit surface AMPA receptors and potentiate excitatory postsynaptic currents. We present evidence that a Rac1-JNK1 signaling pathway mediates ser-295 phosphorylation and regulates synaptic content of PSD-95. Ser-295 phosphorylation is suppressed by chronic elevation, and increased by chronic silencing, of synaptic activity. Rapid dephosphorylation of ser-295 occurs in response to NMDA treatment that causes chemical long-term depression (LTD). Overexpression of a phosphomimicking mutant (S295D) of PSD-95 inhibited NMDA-induced AMPA receptor internalization and blocked the induction of LTD. The data suggest that synaptic strength can be regulated by phosphorylation-dephosphorylation of ser-295 of PSD-95 and that synaptic depression requires the dephosphorylation of ser-295.

We demonstrate the continued growth of single-walled carbon nanotubes (SWNTs) from ordered arrays of open-ended SWNTs in a way analogous to epitaxy. Nanometer-sized metal catalysts were docked to the SWNT open ends and subsequently activated to restart growth. SWNTs thus grown inherit the diameters and chirality from the seeded SWNTs, as indicated by the closely matched frequencies of Raman radial breathing modes before and after the growth.