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Fig. 1 | Molecular Autism

Fig. 1

From: Disruption of grin2B, an ASD-associated gene, produces social deficits in zebrafish

Fig. 1

Zebrafish orthologues have a similar sequence and function to human GluN2B (hGluN2B) A Schematic depiction of membrane topology of two NMDAR subunits. Functional NMDARs are tetramers composed of two obligatory GluN1 subunits and typically two GluN2 (AD) subunits. NMDARs are composed of four modular domains: the extracellular ATD and LBD; the membrane-embedded TMD; and the intracellular CTD. These domains are intrinsic to the full-length receptor as well as individual subunits. Each individual subunit contributes three transmembrane segments (M1, M3, and M4) and a M2 pore loop to form the ion channel. B Linear representation of an NMDAR subunit. Colors match the 3D cartoon in (A) with TMD-associated linkers indicated in blue. The S1 and S2 combine to generate the LBD, which in the 3-dimensional structure is referred to as D1 (mainly composed of S1) and D2 (mainly composed of S2). Table, broken down by NMDAR region, showing the amino acid alignment between hGluN2B and each of the zebrafish GluN2B paralogues (zGluN2Ba and zGluN2Bb). Values indicate percent similarity of amino acids. C Whole-cell currents from HEK 293 cells expressing human GluN1 subunit (hGluN1), with either hGluN2B (hGluN1/hGluN2B) (left panel) or the zGluN2Bb (hGluN1/zGluN2Bb) (right panel) Currents were elicited by a 2.5 s application of glutamate (1 mM, gray bar) in the continuous presence of glycine (0.1 mM). Holding potential, − 70 mV. D Variations in peak current amplitudes between the constructs. Bar graph (mean ± SEM) showing peak current amplitude density (Ipeak/Membrane capacitance). Circles are individual recordings. Number of recordings are 11 and 12 (left to right). E Whole-cell currents in response to brief (2 ms) glutamate applications, as occurs at synapses. F Bar graph (mean ± SEM) showing deactivation rates. Values were not significantly different. Number of recordings are 11 and 12 (left to right)

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