Correction: Ankyrin-G regulates forebrain connectivity and network synchronization via interaction with GABARAP

Nelson, Arin D.; Caballero‐Florán, Rene Nahum; Diaz, Jonmarcos; Hull, Jacob M.; Yuan, Ying; Li, J.; Chen, K.; Walder, Kathryn K.; Lopez-Santiago, Luis F.; Bennett, Victor Manuel; McInnis, Melvin G.; Isom, Lori L.; Wang, Chao; Zhang, Mingjie; Jones, Kelly; Jenkins, Paul M.

doi:10.1038/s41380-019-0361-0

Cited by 3 publications

(2 citation statements)

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“…Na V 1.2 channels are expressed on both the somatic and dendritic membrane of mature neocortical pyramidal neurons. Data shown above indicate that ankyrin-B is important for dendritic Na V scaffolding; however, previous reports have demonstrated that both ankyrin-B and ankyrin-G are present on the soma of mature pyramidal neurons (Jenkins et al, 2015;Nelson et al, 2019;Tseng et al, 2015). As such, Ank2 haploinsufficiency is expected to impair measures of dendritic excitability, but whether somatic excitability is also affected may depend instead on how channels interact with ankyrin-G at the soma.…”

Section: Ank2 Haploinsufficiency Impairs Dendritic But Not Somatic Ex...mentioning

confidence: 89%

Physical and functional convergence of the autism risk genesScn2aandAnk2in neocortical pyramidal cell dendrites

Nelson

Catalfio

Philippe

et al. 2022

Preprint

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Dysfunction in sodium channels and their ankyrin scaffolding partners have both been implicated in neurodevelopmental disorders, including autism spectrum disorder (ASD). In particular, the genes SCN2A, which encodes the sodium channel NaV1.2, and ANK2, which encodes ankyrin-B, have strong ASD association. Recent studies indicate that ASD-associated haploinsufficiency in Scn2a impairs dendritic excitability and synaptic function in neocortical pyramidal cells, but how NaV1.2 is anchored within dendritic regions is unknown. Here, we show that ankyrin-B is essential for scaffolding NaV1.2 to the dendritic membrane of mouse neocortical neurons, and that haploinsufficiency of Ank2 phenocopies intrinsic dendritic excitability and synaptic deficits observed in Scn2a+/- conditions. Thus, these results establish a direct, convergent link between two major ASD risk genes and reinforce an emerging framework suggesting that neocortical pyramidal cell dendritic dysfunction can be etiological to neurodevelopmental disorder pathophysiology.

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Section: Ank2 Haploinsufficiency Impairs Dendritic But Not Somatic Ex...mentioning

confidence: 89%

Physical and functional convergence of the autism risk genesScn2aandAnk2in neocortical pyramidal cell dendrites

Nelson

Catalfio

Philippe

et al. 2022

Preprint

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“…For staining perisomatic GABAergic synapses, antigen retrieval was conducted in 10 µM sodium citrate for 20 min at 95°C (41). After a brief rinse in PBS, the slices were blocked in blocking buffer (1x PBS, 0.3% Triton x-100, 3% normal donkey serum, 0.05 % sodium azide) for 1 hour at room temperature (RT), and then incubated with the following primary antibodies in the blocking solution at 4°C overnight: mouse anti-Bassoon (SAP7F407; 1:1,000; ENZO), G.P.…”

Section: Methodsmentioning

confidence: 99%

Dscamgene triplication causes neocortical overinhibition in Down syndrome

Liu

Caballero‐Florán

Yang

et al. 2020

Preprint

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A growing number of molecules have been identified as regulators of inhibitory synapse development, but whether dysregulated expression of these molecules contribute to brain disorders is poorly understood. Here we show that Down syndrome cell adhesion molecule (Dscam) regulates the inhibition of neocortical pyramidal neurons (PyNs) in a level-dependent fashion. Loss of Dscam impairs inhibitory neuron development and function.In the Ts65Dn mouse model for Down syndrome, where Dscam is overexpressed, GABAergic innervation of cortical PyNs by chandelier and basket cells is increased. Genetic normalization of Dscam expression rescues the excessive GABAergic innervation and the increased inhibition of PyNs. These findings demonstrate excessive GABAergic innervation and inhibition in the neocortex of Down syndrome mouse model and identify Dscam overexpression as the cause. They also implicate dysregulated Dscam levels as a potential pathogenic driver in related neurological disorders. Dscam| Down syndrome| GABAergic| synapse| chandelier cells| basket cells| Neocortex| Ts65Dn

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Spectrin-beta 2 facilitates the selective accumulation of GABAA receptors at somatodendritic synapses

Smalley

Cho

et al. 2023

Commun Biol

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Fast synaptic inhibition is dependent on targeting specific GABAAR subtypes to dendritic and axon initial segment (AIS) synapses. Synaptic GABAARs are typically assembled from α1-3, β and γ subunits. Here, we isolate distinct GABAARs from the brain and interrogate their composition using quantitative proteomics. We show that α2-containing receptors co-assemble with α1 subunits, whereas α1 receptors can form GABAARs with α1 as the sole α subunit. We demonstrate that α1 and α2 subunit-containing receptors co-purify with distinct spectrin isoforms; cytoskeletal proteins that link transmembrane proteins to the cytoskeleton. β2-spectrin was preferentially associated with α1-containing GABAARs at dendritic synapses, while β4-spectrin was associated with α2-containing GABAARs at AIS synapses. Ablating β2-spectrin expression reduced dendritic and AIS synapses containing α1 but increased the number of synapses containing α2, which altered phasic inhibition. Thus, we demonstrate a role for spectrins in the synapse-specific targeting of GABAARs, determining the efficacy of fast neuronal inhibition.

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Correction: Ankyrin-G regulates forebrain connectivity and network synchronization via interaction with GABARAP

Cited by 3 publications

References 0 publications

Physical and functional convergence of the autism risk genesScn2aandAnk2in neocortical pyramidal cell dendrites

Physical and functional convergence of the autism risk genesScn2aandAnk2in neocortical pyramidal cell dendrites

Dscamgene triplication causes neocortical overinhibition in Down syndrome

Spectrin-beta 2 facilitates the selective accumulation of GABAA receptors at somatodendritic synapses

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