The actin-spectrin submembrane scaffold restricts endocytosis along proximal axons

• 成果类型: Article
• 署名作者: Wernert, Florian; Moparthi, Satish Babu; Pelletier, Florence; Laine, Jeanne; Simons, Eline; Moulay, Gilles; Rueda, Fanny; Jullien, Nicolas; Benkhelifa-Ziyyat, Sofia; Papandreou, Marie-Jeanne; Leterrier, Christophe; Vassilopoulos, Stephane
• 署名单位: Aix-Marseille Universite; Centre National de la Recherche Scientifique (CNRS); Institut National de la Sante et de la Recherche Medicale (Inserm); Sorbonne Universite; Sorbonne Universite
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-8740
• DOI: 10.1126/science.ado2032
• 发表日期: 2024-08-23
• 关键词: initial segment; clathrin; microscopy; receptors; DYNAMICS; platform; domain; state

摘要

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.