Nicolas Piguel, Ph.D.
Peter Penzes, Ph.D.
Physiology
Ankyrin-G, synapse, neurons, dendrites, palmitoylation, lithium, bipolar disorder
Third Floor, Feinberg Pavilion, Northwestern Memorial Hospital
Common and rare variants in ANK3, encoding the ankyrin-G protein, have been associated with bipolar disorder, schizophrenia, ASD and intellectual disability. Several protein isoforms have been described with different functions in neurons. Ankyrin-G has been studied extensively in the axon initial segment (AIS), where the 480 kDa and 270 kDa isoforms maintain axo-dendritic polarity and the AIS by establishing a diffusion barrier. AnkG also plays a role in stabilizing node of Ranvier and GABAergic synapses. Our previous work showed that 190 kDa AnkG can form nanodomains in dendritic spines to regulate AMPA receptor stability and activity-dependent spine enlargement. Here, we provide evidence that palmitoylation at amino acid residue C70 is necessary for proper AnkG190 spine localization, spine formation and composition. Our data suggest a specific role in dendrite maintenance of the palmitoylated 190 kDa isoform in excitatory neurons. Finally, we show than lithium treatment, a mood-stabilizer, can rescue AnkG knock down dendrite effect.