Language
English
Publication Date
10-27-2026
Journal
Cell Reports
DOI
10.1016/j.celrep.2026.118084
PMID
42826098
Abstract
Neurodegenerative disease is marked not just by loss of proteins or cells, but by dynamic rewiring of macromolecular interaction networks that precede and drive pathology. Here, we present a temporally resolved, systems-scale map of multi-protein complex remodeling in a tauopathy model, integrating co-fractionation mass spectrometry, quantitative phosphoproteomics, and machine learning to decode phosphorylation-dependent shifts in protein interactomes across disease progression. This interactomic atlas serves as a resource to investigate functional assemblies, including MAPT-Dpysl2 and Cyfip1-actin, as well as ptk2b-Kars/Dars and ptk2b-Msn-Farsb-complexes, that modulate early disease phenotypes in vivo. Notably, it captures the composition, dynamics, and regulatory state of protein complexes at scale. By revealing how phosphorylation tunes macromolecular complex architecture and function, this work highlights dynamic network instability that develops over the course of tauopathy, and establishes a generalizable framework for mechanistic dissection of functional complexes in neurodegeneration.
Keywords
Animals, Tauopathies, Protein Interaction Maps, Mice, Disease Models, Animal, Phosphorylation, tau Proteins, Proteomics, Humans, Alzheimer’s disease; CP: neuroscience; multiplex co-fractionation mass spectrometry; network remodeling; neurodegeneration; phosphoproteomics; protein interactome; systems proteomics; tauopathy
Published Open-Access
yes
Recommended Citation
Lin, Weiwei; Phanse, Sadhna; van der Spek, Sophie J F; et al., "Progressive Remodeling of Global Protein Interaction Networks in a Mouse Model of Tauopathy" (2026). Faculty, Staff and Students Publications. 8541.
https://digitalcommons.library.tmc.edu/baylor_docs/8541