Genes 2 Brains 2 Mind 2 Me

“A devil, a born devil, on whose nature
Nurture can never stick; on whom my pains,
Humanely taken, all, all lost, quite lost
And as with age his body uglier grows,
So his mind cankers.”

So says the wizard Prospero about the wretched Caliban in Shakespeare’s The Tempest (Act IV, Scene I, lines 188 – 192).  Although Shakespeare was not a neuroscientist (more to his credit!), his poignant phrase, “on whose nature, Nurture can never stick”  strikes the very core of the modern debates on the role of genes and personal genomes, and perhaps reminds us that our human experience is delicately balanced amidst the interaction of genes and environment.

Among the some 20,500 genes in the human genome (yes, this is the latest estimate from Eric Lander this past weekend) one particularly amazing gene stands out.   CACNA2D1 the alpha-2/delta-1 subunit of the voltage-dependent calcium channel complex (which also binds to the widely-prescribed drug Gabapentin) encodes a protein who, in conjunction with other related subunits, forms a calcium channel to mediate the influx of calcium ions into neurons when membrane polarization occurs.  In the recent article, “Gabapentin Receptor α2δ-1 Is a Neuronal Thrombospondin Receptor Responsible for Excitatory CNS Synaptogenesis” [doi:10.1016/j.cell.2009.09.025] Eroglu and colleagues reveal that this single gene – initiates the development of synapses – the dynamic structures whose ever changing interconnections make us who we are – that allow “nurture to stick” as it were.

More on the biology of CACNA2D1 and its interactions with its ligand – Thrombospondins – to come.