SynGAP is a Ras/Rap GTPase-activating protein (GAP) that is a major constituent of postsynaptic densities (PSDs) from mammalian forebrain. Its α1 isoform binds to all three PDZ (PSD-95, Discs-large, ZO-1) domains of PSD-95, the principal PSD scaffold, and can occupy as many as 15% of these PDZ domains. We present evidence that synGAP-α1 regulates the composition of the PSD by restricting bindin...

The synaptic protein PSD-95/SAP90 binds to and clusters a variety of membrane proteins via its two N-terminal PDZ domains. We report a novel protein, CRIPT, which is highly conserved from mammals to plants and binds selectively to the third PDZ domain (PDZ3) of PSD-95 via its C terminus. While conforming to the consensus PDZ-binding C-terminal sequence (X-S/T-X-V-COOH), residues at the -1 posit...

1 SynGAP is a Ras/Rap GTPase-activating protein (GAP) present in high concentration in postsynaptic 2 densities (PSDs) from mammalian forebrain where it binds to all three PDZ (PSD-95, Discs-large, ZO-1) 3 domains of PSD-95. We show that phosphorylation of synGAP by Ca 2+ /calmodulin-dependent protein 4 kinase II (CaMKII) decreases its affinity for the PDZ domains as much as 10-fold, measured b...

The postsynaptic density (PSD) is a massive multi-protein complex whose functions include positioning signalling molecules for induction of long-term potentiation (LTP) and depression (LTD) of synaptic strength. These processes are thought to underlie memory formation. To understand how the PSD coordinates bidirectional synaptic plasticity with different synaptic activation patterns, it is nece...

Post-stroke depression (PSD) affects approximately one-third of all stroke patients. It hinders rehabilitation and is associated with worse functional outcome and increased mortality. Since the identification of PSD is a significant clinical problem, clinicians and researchers have tried to identify predictors that indicate patients at risk of developing PSD. This also includes the research que...

The calcium-dependent protease calpain cleaves the NMDA receptor 2 (NR2) subunit of the NMDA receptor both in vitro and in vivo and thus potentially modulates NMDA receptor function and turnover. We examined the ability of postsynaptic density-95 (PSD-95) protein to alter the calpain-mediated cleavage of NR2A and NR2B. Coexpression of PSD-95 with NMDA receptors in human embryonic kidney 293 cel...

Clustering of Kv1 channels at the juxtaparanodal region (JXP) in myelinated axons depends on their association with the Caspr2/TAG-1 adhesion complex. The interaction between these channels and Caspr2 was suggested to depend on PDZ (PSD-95/Discs large/zona occludens-1) scaffolding proteins. Here, we show that at a subset of the JXP, PSD-93 colocalizes with Caspr2, K(+) channels and its related ...

Myristoylated alanine-rich C kinase substrate (MARCKS) is an unfolded protein that contains well characterized actin-binding sites within the phosphorylation site domain (PSD), yet paradoxically, we now find that intact MARCKS does not bind to actin. Intact MARCKS also does not bind as well to calmodulin as does the PSD alone. Myristoylation at the N terminus alters how calmodulin binds to MARC...

The neurochemical changes that occur in the brain of patients with post-stroke depression (PSD) are not fully understood. This study aims to explore the correlation between cerebellar metabolism changes and PSD using proton magnetic resonance spectroscopy (1H-MRS). Participants were assigned to 3 groups: 60 patients with PSD (PSD group), 60 stroke patients without depression (NOPSD group), and ...

OBJECTIVES Inflammatory cytokines are implicated in the pathophysiology of both stroke and depression, and their production is influenced by the transcriptional activity of particular gene polymorphisms. We hypothesised that alleles related to higher pro-inflammatory and/or lower anti-inflammatory cytokine production would be associated with post-stroke depression (PSD). METHODS In 276 stroke...