Endocytosis in the axon initial segment: Roles in neuronal polarity and plasticity

The axon initial segment (AIS) is a specialized domain that maintains neuronal polarity and is the site of action potential generation, both of which underlie the neuron's ability to send and receive signals. Disruption of the AIS leads to a loss of neuronal polarity, altered neuronal signaling, and an array of neurological disorders. Therefore, understanding how the AIS forms and functions is a central question in cellular neuroscience that is essential to understanding neuronal physiology. Decades of study have identified many molecular components and mechanisms at the AIS. Recently, endocytosis at the AIS has been identified to function in both maintaining neuronal polarity and in mediating AIS plasticity through its ability to dynamically remodel the plasma membrane composition. This review discusses the emerging evidence for the roles of endocytosis in regulating AIS function and structural insights into how endocytosis can occur at the AIS.