Structure of transmembrane AMPA receptor regulatory protein subunit γ2.

Transmembrane AMPA receptor regulatory proteins (TARPs) are claudin-like proteins that tightly regulate AMPA receptors (AMPARs) and are fundamental for excitatory neurotransmission. With cryo-electron microscopy (cryo-EM) we reconstruct the 36 kDa TARP subunit γ2 to 2.3 Å, which points to structural diversity among TARPs.

Syngap1 and the development of murine neocortical progenitor cells.

SYNGAP1 is a major regulator of synaptic plasticity through its interaction with synaptic scaffold proteins and modulation of Ras and Rap GTPase signaling pathways. mutations in humans are often associated with intellectual disability, epilepsy, and autism spectrum disorder. heterozygous loss-of-function results in impaired LTP, premature maturation of dendritic spines, learning disabilities and seizures in mice.

WWC2 modulates GABA-receptor-mediated synaptic transmission, revealing class-specific mechanisms of synapse regulation by WWC family proteins.

The WW and C2 domain-containing protein (WWC2) is implicated in several neurological disorders. Here, we demonstrate that WWC2 interacts with inhibitory, but not excitatory, postsynaptic scaffolds, consistent with prior proteomic identification of WWC2 as a putative component of the inhibitory postsynaptic density. Using mice lacking WWC2 expression in excitatory forebrain neurons, we show that WWC2 suppresses γ-aminobutyric acid type-A receptor (GABAR) incorporation into the plasma membrane and regulates HAP1 and GRIP1, which form a complex promoting GABAR recycling to the membrane.

Calcium-permeable AMPA receptors govern PV neuron feature selectivity.

The brain helps us survive by forming internal representations of the external world. Excitatory cortical neurons are often precisely tuned to specific external stimuli. However, inhibitory neurons, such as parvalbumin-positive (PV) interneurons, are generally less selective.

Context-dependent hyperactivity in and zebrafish models of SYNGAP1-related disorder.

Background And Aims: SYNGAP1-related disorder (SYNGAP1-RD) is a prevalent genetic form of Autism Spectrum Disorder and Intellectual Disability (ASD/ID) and is caused by or inherited mutations in one copy of the gene. In addition to ASD/ID, SYNGAP1 disorder is associated with comorbid symptoms including treatment-resistant-epilepsy, sleep disturbances, and gastrointestinal distress. Mechanistic links between these diverse symptoms and variants remain obscure, therefore, our goal was to generate a zebrafish model in which this range of symptoms can be studied.