An autism-associated calcium channel variant causes defects in neuronal polarity in the ALM neuron of C. elegans.

Buddell, Tyler; Quinn, Christopher C.

doi:10.17912/micropub.biology.000378

Cited by 6 publications

(3 citation statements)

References 12 publications

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“…Timothy syndrome is a syndromic form of autism that can be caused by either of three rare de novo mutations in CACNA1C (Bader et al, 2011). Meanwhile, a gain-of-function egl-19 mutation, which is equivalent to the Timothy syndrome mutation in CACNA1C, causes defects in axon termination and neuronal polarity in the ALM neuron of C. elegans (Buddell and Quinn, 2021). Our results showed that the reduced-function mutation of egl-19 results in longer processes and longer soma in both glia and neurons.…”

Section: Discussionmentioning

confidence: 99%

“…A previous study reported that gain-of-function mutations of egl-19 cause the growth of an ectopic process from the cell body of the ALM neurons (Buddell and Quinn, 2021). To better understand the phenotype of egl-19 in olfaction, we labeled ASH neurons with GFP and checked the morphology by confocal microscopy.…”

Section: Dysfunction Of Egl-19 Causes Longer Soma and Processes In Bo...mentioning

confidence: 99%

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The Voltage-Gated Calcium Channel EGL-19 Acts on Glia to Drive Olfactory Adaptation

Cheng

Liu

et al. 2022

Front. Mol. Neurosci.

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Calcium channelopathies have been strongly linked to cardiovascular, muscular, neurological and psychiatric disorders. The voltage-gated calcium channels (VGCC) are vital transducers of membrane potential changes to facilitate the dynamics of calcium ions and release of neurotransmitter. Whether these channels function in the glial cell to mediate calcium variations and regulate behavioral outputs, is poorly understood. Our results showed that odorant and mechanical stimuli evoked robust calcium increases in the amphid sheath (AMsh) glia from C. elegans, which were largely dependent on the L-Type VGCC EGL-19. Moreover, EGL-19 modulates the morphologies of both ASH sensory neurons and AMsh glia. Tissue-specific knock-down of EGL-19 in AMsh glia regulated sensory adaptability of ASH neurons and promoted olfactory adaptation. Our results reveal a novel role of glial L-Type VGCC EGL-19 on olfaction, lead to improved understanding of the functions of VGCCs in sensory transduction.

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Section: Discussionmentioning

confidence: 99%

Section: Dysfunction Of Egl-19 Causes Longer Soma and Processes In Bo...mentioning

confidence: 99%

The Voltage-Gated Calcium Channel EGL-19 Acts on Glia to Drive Olfactory Adaptation

Cheng

Liu

et al. 2022

Front. Mol. Neurosci.

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“…For example, loss of the frizzled receptor or the extracellular Wnt ligand creates a multipolar phenotype in the ALM [32,33]. The ALM has also been used to study several other receptors, channels, and intracellular signaling proteins that can polarize axon growth [34][35][36][37][38][39][40][41].…”

Section: Unc-6 and Slt-1 Extracellular Guidance Cues Polarize Alm Axo...mentioning

confidence: 99%

The ANC-1 (Nesprin-1/2) organelle-anchoring protein functions through mitochondria to polarize axon growth in response to SLT-1

et al. 2022

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A family of giant KASH proteins, including C. elegans ANC-1 and mammalian Nesprin-1 and -2, are involved in organelle anchoring and are associated with multiple neurodevelopmental disorders including autism, bipolar disorder, and schizophrenia. However, little is known about how these proteins function in neurons. Moreover, the role of organelle anchoring in axon development is poorly understood. Here, we report that ANC-1 functions with the SLT-1 extracellular guidance cue to polarize ALM axon growth. This role for ANC-1 is specific to its longer ANC-1A and ANC-1C isoforms, suggesting that it is mechanistically distinct from previously described roles for ANC-1. We find that ANC-1 is required for the localization of a cluster of mitochondria to the base of the proximal axon. Furthermore, genetic and pharmacological studies indicate that ANC-1 functions with mitochondria to promote polarization of ALM axon growth. These observations reveal a mechanism whereby ANC-1 functions through mitochondria to polarize axon growth in response to SLT-1.

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Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function

Ntoulas,

Brakatselos,

Nakas

et al. 2024

Transl Psychiatry

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Fragile X syndrome (FXS) is the most common cause of inherited intellectual disabilities and the most prevalent monogenic cause of autism. Although the knockout (KO) of the Fmr1 gene homolog in mice is primarily used for elucidating the neurobiological substrate of FXS, there is limited association of the experimental data with the pathophysiological condition in humans. The use of Fmr1 KO rats offers additional translational validity in this regard. Therefore, we employed a multi-level approach to study the behavioral profile and the glutamatergic and GABAergic neurotransmission status in pathophysiology-associated brain structures of Fmr1 KO rats, including the recordings of evoked and spontaneous field potentials from hippocampal slices, paralleled with next-generation RNA sequencing (RNA-seq). We found that these rats exhibit hyperactivity and cognitive deficits, along with characteristic bidirectional glutamatergic and GABAergic alterations in the prefrontal cortex and the hippocampus. These results are coupled to affected excitability and local inhibitory processes in the hippocampus, along with a specific transcriptional profile, highlighting dysregulated hippocampal network activity in KO rats. Overall, our data provide novel insights concerning the biobehavioral profile of FmR1 KO rats and translationally upscales our understanding on pathophysiology and symptomatology of FXS syndrome.

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An autism-associated calcium channel variant causes defects in neuronal polarity in the ALM neuron of C. elegans.

Cited by 6 publications

References 12 publications

The Voltage-Gated Calcium Channel EGL-19 Acts on Glia to Drive Olfactory Adaptation

The Voltage-Gated Calcium Channel EGL-19 Acts on Glia to Drive Olfactory Adaptation

The ANC-1 (Nesprin-1/2) organelle-anchoring protein functions through mitochondria to polarize axon growth in response to SLT-1

Multi-level profiling of the Fmr1 KO rat unveils altered behavioral traits along with aberrant glutamatergic function

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