Paralemmin-1 controls the nanoarchitecture of the neuronal submembrane cytoskeleton

• DOI: 10.1126/sciadv.adt3724
• Publication Date: 2025-03-07T18:59:41Z
• Authors: Victor Macarrón-P...; Jasmine Hubrich; Maria Augusta do ...; Nicole G. Metzendorf; Simon Kneilmann; Marleen Trapp; Claudio Acuna; Annarita Patrizi; Elisa D’Este; Manfred W. Kilimann
• Keywords: Ankyrin

The submembrane cytoskeleton of neurons displays a highly ordered 190-nanometer periodic actin-spectrin lattice, the membrane-associated skeleton (MPS). It is involved in mechanical resilience, signaling, and action potential transmission. Here, we identify paralemmin-1 (Palm1) as component regulator MPS. Palm1 binds to amino-terminal region βII-spectrin, MINFLUX microscopy localizes it close proximity (<20 nanometers) actin-capping protein MPS adducin. Combining overexpression, knockout, rescue experiments, observe that expression level controls degree periodicity also affects electrophysiological properties neurons. A single amino acid mutation (W54A) abolishes binding remodeling activities Palm1. Our findings specifically dedicated organizing will advance understanding assembly plasticity general.