Conjugation of peptides to the passivation shell of gold nanoparticles for targeting of cell-surface receptors.

We report the preparation of gold nanoparticles (AuNPs) functionalized with the peptide-toxin conantokin-G and their selective binding to N-methyl-d-aspartate (NMDA) receptors recombinantly expressed by transfected HEK 293 cells. The AuNPs are passivated with a mixed self-assembled monolayer of ω-carboxy- and ω-amino-polyethylene glycol (PEG) thiols. We compare two different passivation systems: the alkyl-PEG600 system is characterized by a C(11)-alkyl chain between the thiol group and the PEG segment, whereas the PEG3000 system lacks this alkyl-chain.

Synaptic activity and nuclear calcium signaling protect hippocampal neurons from death signal-associated nuclear translocation of FoxO3a induced by extrasynaptic N-methyl-D-aspartate receptors.

Synaptic activity and the generation of nuclear calcium signals promote neuronal survival through a transcription-dependent process that is not fully understood. Here we show that one mechanism of activity-induced acquired neuroprotection involves the Forkhead transcription factor, FoxO3a, which is known to induce genomic death responses upon translocation from the cytosol to the nucleus. Depletion of endogenous FoxO3a using RNA interference renders hippocampal neurons more resistant to excitotoxic cell death.

A quantitative method to assess extrasynaptic NMDA receptor function in the protective effect of synaptic activity against neurotoxicity.

Background: Extrasynaptic NMDA receptors couple to a CREB shut-off pathway and cause cell death, whereas synaptic NMDA receptors and nuclear calcium signaling promote CREB-mediated transcription and neuronal survival. The distribution of NMDA receptors (synaptic versus extrasynaptic) may be an important parameter that determines the susceptibility of neurons to toxic insults. Changes in receptor surface expression towards more extrasynaptic NMDA receptors may lead to neurodegeneration, whereas a reduction of extrasynaptic NMDA receptors may render neurons more resistant to death.

The postsynaptic scaffold proteins ProSAP1/Shank2 and Homer1 are associated with glutamate receptor complexes at rat retinal synapses.

The postsynaptic density (PSD) at glutamatergic synapses is a macromolecular complex of various molecules that organize the different glutamate receptors spatially and link them to their appropriate downstream signaling pathways and to the cytoskeleton. Recently, a new family of multidomain proteins called Shanks or ProSAPs (proline-rich synapse-associated proteins) has been identified. They are suggested to be central adaptor proteins of the PSD of glutamatergic synapses, bridging different types of glutamate receptor complexes.

The presynaptic active zone protein bassoon is essential for photoreceptor ribbon synapse formation in the retina.

The photoreceptor ribbon synapse is a highly specialized glutamatergic synapse designed for the continuous flow of synaptic vesicles to the neurotransmitter release site. The molecular mechanisms underlying ribbon synapse formation are poorly understood. We have investigated the role of the presynaptic cytomatrix protein Bassoon, a major component of the photoreceptor ribbon, in a mouse retina deficient of functional Bassoon protein.