Endocytosis in the axon initial segment is a clearance mechanism to maintain neuronal polarity

Nature (2022)

Eichel K, Uenaka T, Belapurkar V, Lu R, Cheng S, Pak JS, Taylor CA, Südhof TC, Malenka RC, Wernig M, Özkan E, Perrais D, Shen K

Neurons are highly polarized cells that face a fundamental challenge of compartmentalizing a vast and diverse repertoire of proteins in order to function properly. The axon initial segment (AIS) is a specialized domain separating a neuron’s morphologically, biochemically, and functionally distinct axon and dendrite compartments. How the AIS maintains polarity between these compartments is not fully understood. Therefore, endocytic removal of polarized receptors that diffuse into the AIS serves as a membrane clearance mechanism that likely works in conjunction with the known AIS diffusion barrier to maintain neuronal polarity on the plasma membrane. Our results reveal a conserved endocytic clearance mechanism in the AIS to maintain neuronal polarity by reinforcing axonal and dendritic compartment boundaries.