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bioRxiv · 10.1101/2020.09.11.292003

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

Buddell, T.·Quinn, C. C.
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Abstract

Variants of the CACNA1C voltage-gated calcium channel gene have been associated with autism and other neurodevelopmental disorders including bipolar disorder, schizophrenia, and ADHD. The Timothy syndrome mutation is a rare de novo gain-of-function variant in CACNA1C that causes autism with high penetrance, providing a powerful avenue into investigating the role of CACNA1C variants in neurodevelopmental disorders. In our previous work, we demonstrated that an egl-19(gof) mutation, that is equivalent to the Timothy syndrome mutation in the human homolog CACNA1C, can disrupt termination of the PLM axon in C. elegans. Here, we find that the egl-19(gof) mutation disrupts the polarity of process outgrowth in the ALM neuron of C. elegans. We also find that the egl-19(gof) mutation can disrupt termination of the ALM axon. These results suggest that the Timothy syndrome mutation can disrupt multiple steps of axon development. Further work exploring the molecular mechanisms that underlie these perturbations in neuronal polarity and axon termination will give us better understanding to how variants in CACNA1C contribute to the axonal defects that underlie autism.

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Buddell, T., Quinn, C. C.. 2020-09-12. An autism-associated calcium channel variant causes defects in neuronal polarity and axon termination in the ALM neuron of C. elegans. https://doi.org/10.1101/2020.09.11.292003

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