The CACNA1A gene encodes the alpha or main core-forming subunit of the P/Q-type voltage-gated calcium channel, Cav2.1. It also codes in the same messenger RNA for a transcription factor we have named alpha1ACT. Mutations in this gene have been associated with numerous neurological disorders, including: Spinocerebellar ataxia type 6, episodic ataxia, type 2 (EA2), Familial hemiplegic migraine type 1 (FHM1), and various forms of epilepsy such as early infantile epileptic encephalopathy 42 (EIEE42).  There has never been a strict relationship between the type of mutation and a type of syndrome. Therefore, to develop treatments in the future, there will be a need for a more detailed explanation of the disease mechanisms and better genotype-phenotype correlation.

Expression of CACNA1A and a potential therapeutic strategy are outlined in the image below.
Figure by Dr. Sally-Jane Rowland. Find her research profile here

Our efforts in this program are to define the relationship between the mutant channel function and the action of the transcription factor alpha1ACT. We hypothesize that defects in the channel function can affect both channel gating and behavior of alpha1ACT in the brain leading to changes in gene expression at critical developmental periods. We are exploring the coupling of calcium channel activity and transcription factor action in a wide range of cellular and animal systems.

To learn more, read our Neuron publication.
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