Unraveling the nanoscale architecture and multifunctional roles of the neuronal membrane skeleton with super-resolution imaging
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Ruobo Zhou, PhD (Penn State University) Host: Kaushik Ragunathan Abstract: Super-resolution fluorescence imaging has transformed our ability to visualize the molecular organization of cells at nanometer scales, providing unprecedented insights into nanoscale architecture, molecular interactions, and cellular function. Yet, imaging complex molecular assemblies over extended timescales and across multiple protein species remains challenging. We recently developed FLEXTAG, a compact, self-renewable, anti- photobleaching protein-labeling platform that enables multiplexed and sustained super- resolution imaging. We applied these approaches to the neuronal membrane-associated periodic skeleton (MPS), a well-defined nanoscale cytoskeletal architecture that provides a powerful model system for understanding how molecular organization at the nanoscale shapes cellular function. The MPS, composed of actin, spectrin, and associated molecules, forms a lattice-like cortical structure whose molecular composition and functions have remained incompletely understood. Using co-immunoprecipitation and mass spectrometry, we identified hundreds of candidate MPS-interacting proteins spanning diverse functional categories. Super-resolution imaging of representative proteins, including previously unknown structural components, motor proteins, cell adhesion molecules (CAMs), ion channels, and signaling proteins, revealed periodic distributions characteristic of the MPS along neurites. Genetic perturba
