Regulation of neuronal ankyrin localization and function by post-translational modifications

Ankyrins are a family of intracellular scaffolding proteins that control the subcellular localization of a host of critically important signaling proteins within neurons, including many proteins associated with neurological disease. Ankyrin proteins are a vital component of the neuron. These scaffolding proteins must be spatially and temporally arranged to interact with their binding partners and facilitate proper neuronal signaling. Dysfunction of ankyrins is associated with neurodevelopmental disorders such as epilepsy and autism spectrum disorder. Despite the high degree of sequence similarity between ankyrin proteins, they display almost completely nonoverlapping localization and function. How ankyrins localize to the correct subcellular compartments to interact with their binding partners and complete their distinct roles remains poorly understood. Emerging evidence suggests that post-translational modifications may play a key part in this process. Some of the post-translational modifications that have been identified to regulate ankyrins are phosphorylation, ubiquitination, and palmitoylation. These modifications affect proper interactions, function, and localization of ankyrin proteins, which highlights their potential role in disease. This review will give an overview of neuronal ankyrins, and how post-translational modifications could be utilized to regulate protein localization and function in the context of neurological disease.