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The actin-spectrin submembrane scaffold restricts endocytosis along proximal axons

Affiliations
  • 1Aix Marseille Université, CNRS, INP UMR7051, NeuroCyto, 13005 Marseille, France.
  • 2Sorbonne Université, INSERM, Institute of Myology, Centre of Research in Myology, UMRS 974, Paris, France.
  • 3Sorbonne Université, Department of Physiology, Faculty of Medicine Pitié-Salpêtrière, Paris, France.

Published on:

August 22, 2024

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.

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