TY  - JOUR
AU  - Macarrón-Palacios, Victor
AU  - Hubrich, Jasmine
AU  - do Rego Barros Fernandes Lima, Maria Augusta
AU  - Metzendorf, Nicole G
AU  - Kneilmann, Simon
AU  - Trapp, Marleen
AU  - Acuna, Claudio
AU  - Patrizi, Annarita
AU  - D'Este, Elisa
AU  - Kilimann, Manfred W
TI  - Paralemmin-1 controls the nanoarchitecture of the neuronal submembrane cytoskeleton.
JO  - Science advances
VL  - 11
IS  - 10
SN  - 2375-2548
CY  - Washington, DC [u.a.]
PB  - Assoc.
M1  - DKFZ-2025-00504
SP  - eadt3724
PY  - 2025
N1  - DKFZ-ZMBH Alliance
AB  - The submembrane cytoskeleton of neurons displays a highly ordered 190-nanometer periodic actin-spectrin lattice, the membrane-associated periodic skeleton (MPS). It is involved in mechanical resilience, signaling, and action potential transmission. Here, we identify paralemmin-1 (Palm1) as a component and regulator of the MPS. Palm1 binds to the amino-terminal region of βII-spectrin, and MINFLUX microscopy localizes it in close proximity (<20 nanometers) to the actin-capping protein and MPS component adducin. Combining overexpression, knockout, and rescue experiments, we observe that the expression level of Palm1 controls the degree of periodicity of the MPS and also affects the electrophysiological properties of neurons. A single amino acid mutation (W54A) in Palm1 abolishes the MPS binding and remodeling activities of Palm1. Our findings identify Palm1 as a protein specifically dedicated to organizing the MPS and will advance the understanding of the assembly and plasticity of the actin-spectrin submembrane skeleton in general.
KW  - Neurons: metabolism
KW  - Neurons: cytology
KW  - Cytoskeleton: metabolism
KW  - Animals
KW  - Protein Binding
KW  - Humans
KW  - Spectrin: metabolism
KW  - Spectrin: genetics
KW  - Actins: metabolism
KW  - Cell Membrane: metabolism
KW  - Cytoskeletal Proteins: metabolism
KW  - Cytoskeletal Proteins: genetics
KW  - Mice
KW  - Spectrin (NLM Chemicals)
KW  - Actins (NLM Chemicals)
KW  - Cytoskeletal Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40053592
C2  - pmc:PMC11887803
DO  - DOI:10.1126/sciadv.adt3724
UR  - https://inrepo02.dkfz.de/record/299563
ER  -