The membrane skeleton is constitutively remodeled in neurons by calcium signaling.

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.