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The actin-spectrin submembrane scaffold restricts endocytosis along proximal axons

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 th...

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Published in:Science (American Association for the Advancement of Science) 2024-08, Vol.385 (6711), p.eado2032
Main Authors: Wernert, Florian, Moparthi, Satish Babu, Pelletier, Florence, Lainé, Jeanne, Simons, Eline, Moulay, Gilles, Rueda, Fanny, Jullien, Nicolas, Benkhelifa-Ziyyat, Sofia, Papandréou, Marie-Jeanne, Leterrier, Christophe, Vassilopoulos, Stéphane
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Language:English
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Summary: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.
ISSN:0036-8075
1095-9203
1095-9203
DOI:10.1126/science.ado2032