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

PMID: 33829152 (view PubMed database entry)
DOI: 10.17912/micropub.biology.000378 (read at publisher's website )

Tyler Buddell, Christopher C Quinn,

Variants of the <i>CACNA1C</i> 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 <i>de novo</i> gain-of-function variant in <i>CACNA1C</i> that causes autism with high penetrance, providing a powerful avenue into investigating the role of <i>CACNA1C</i> variants in neurodevelopmental disorders. In our previous work, we demonstrated that an <i>egl-19(gof)</i> mutation, which is equivalent to the Timothy syndrome mutation in <i>CACNA1C,</i> can disrupt termination of the PLM axon in <i>C. elegans</i>. Here, we report a novel phenotype for the <i>egl-19(gof)</i> mutation, whereby it causes the growth of an ectopic process from the ALM cell body. We also extend our previous results to show that the <i>egl-19(gof)</i> mutation causes axon termination defects not only in the PLM axon, but also in 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 of how variants in <i>CACNA1C</i> contribute to the axonal defects that underlie autism.

MicroPubl Biol (microPublication biology)
[2021, 2021:]

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