Abstract
Oligomerized APP-CTFβ appears to interact selectively with the synaptic membrane environment through coupled protein–lipid effects that may influence excitatory signaling. Combining immunocytochemical observations with coarse-grained membrane simulations, this work shows that APP-CTFβ colocalizes with PIP2 at excitatory presynapses, recruits PIP2 through electrostatic interactions centered on Arg76, and can form membrane-associated oligomeric clusters. These interactions are accompanied by local remodeling of the bilayer, including changes in curvature and a thinning effect near the protein, particularly on the C-terminal side. Together, the results support a model in which APP-CTFβ oligomerization and lipid organization are mechanistically linked and may contribute to the modulation of synaptic excitability.
Fabian Schuhmann
Niels Bohr International Academy, Niels Bohr Institute, University of Copenhagen, Copenhagen, Denmark.
Email LinkedIn Github ResearchGate Orcid