The membrane skeleton is constitutively remodeled in neurons by calcium signaling

• 成果类型: Article
• 署名作者: Heller, Evan; Kurup, Naina; Zhuang, Xiaowei
• 署名单位: Harvard University; Howard Hughes Medical Institute; Harvard University; Harvard University
• 刊物名称: SCIENCE
• ISSN/ISSBN: 0036-13956
• DOI: 10.1126/science.adn6712
• 发表日期: 2025-08-07
• 关键词: protein-kinase-c; axon initial segment; f-actin network; ii spectrin; alpha-ii; nanoscale architecture; periodic cytoskeleton; nervous-system; adducin; phosphorylation

摘要

The membrane skeleton in neurons adopts a periodic lattice structure in which actin filaments, capped by adducin and tropomodulin, form ring-shaped structures connected by spectrin tetramers along neurites. This membrane-associated periodic skeleton (MPS) is important for many neuronal functions. Using live-cell super-resolution imaging, we found that the MPS is surprisingly dynamic, undergoing local disassembly and reformation constitutively in axons. MPS remodeling is driven by calcium signaling, leading to actin-ring destabilization through protein kinase C-mediated adducin phosphorylation and to spectrin degradation by calpain. Formin, an actin-nucleating and -polymerizing enzyme, plays a dual role in MPS remodeling and maintenance. MPS remodeling is enhanced by neuronal activity and functionally facilitates endocytosis. Our results highlight the importance of a dynamic membrane skeletal structure in neuronal function.