Ankyrins: Roles in synaptic biology and pathology

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Ankyrins are broadly expressed adaptors that organize diverse membrane proteins into specialized domains and link them to the sub-membranous cytoskeleton. In neurons, ankyrins are known to have essential roles in organizing the axon initial segment and nodes of Ranvier. However, recent studies have revealed novel functions for ankyrins at synapses, where they organize and stabilize neurotransmitter receptors, modulate dendritic spine morphology and control adhesion to the presynaptic site. Ankyrin genes have also been highly associated with a range of neurodevelopmental and psychiatric diseases, including bipolar disorder, schizophrenia and autism, which all demonstrate overlap in their genetics, mechanisms and phenotypes. This review discusses the novel synaptic functions of ankyrin proteins in neurons, and places these exciting findings in the context of ANK genes as key neuropsychiatric disorder risk-factors.HighlightsAnkyrin proteins link membrane proteins to the submembranous actin cytoskeleton.Ankyrins organize synapses, in addition to their canonical roles in the axon.Dendritic spines rely on ankyrin-G for proper stability and synaptic plasticity.Synaptic functions of ankyrins may contribute to neuropsychiatric diseases.

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