The actin-spectrin submembrane scaffold restricts endocytosis along proximal axons

Science. 2024 Aug 23;385(6711):eado2032. doi: 10.1126/science.ado2032. Epub 2024 Aug 23.

Abstract

Clathrin-mediated endocytosis has characteristic features in neuronal dendrites and presynapses, but how membrane proteins are internalized along the axon shaft remains unclear. We focused on clathrin-coated structures and endocytosis along the axon initial segment (AIS) and their relationship to the periodic actin-spectrin scaffold that lines the axonal plasma membrane. A combination of super-resolution microscopy and platinum-replica electron microscopy on cultured neurons revealed that AIS clathrin-coated pits form within "clearings", circular areas devoid of actin-spectrin mesh. Actin-spectrin scaffold disorganization increased clathrin-coated pit formation. Cargo uptake and live-cell imaging showed that AIS clathrin-coated pits are particularly stable. Neuronal plasticity-inducing stimulation triggered internalization of the clathrin-coated pits through polymerization of branched actin around them. Thus, spectrin and actin regulate clathrin-coated pit formation and scission to control endocytosis at the AIS.

MeSH terms

  • Actin Cytoskeleton / metabolism
  • Actins* / metabolism
  • Animals
  • Axons* / metabolism
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Clathrin* / metabolism
  • Clathrin-Coated Vesicles / metabolism
  • Coated Pits, Cell-Membrane / metabolism
  • Endocytosis*
  • HEK293 Cells
  • Humans
  • Neuronal Plasticity
  • Neurons / metabolism
  • Rats
  • Spectrin* / metabolism

Substances

  • Actins
  • Clathrin
  • Spectrin