Structural organization of the actin-spectrin–based membrane skeleton in dendrites and soma of neurons

Significance Actin, spectrin, and associated molecules form a quasi-1D periodic membrane skeleton in neurons, which organizes membrane proteins in periodic distributions and provides mechanical stability for axons. Here, we provide detailed quantifications of this periodic structure in neurons and show that it develops substantially more slowly in dendrites than in axons. Moreover, we observed a 2D, polygonal lattice structure of these molecules in the somatodendritic compartment. The diverse structural organizations and different developmental courses of the membrane skeleton in different neuronal compartments suggest the membrane skeleton is differentially regulated across these neuronal compartments. The observation of the polygonal lattice structure in cells in addition to erythrocytes suggests a potentially general presence of this structure across diverse cell types. Actin, spectrin, and associated molecules form a membrane-associated periodic skeleton (MPS) in neurons. In the MPS, short actin filaments, capped by actin-capping proteins, form ring-like structures that wrap around the circumference of neurites, and these rings are periodically spaced along the neurite by spectrin tetramers, forming a quasi-1D lattice structure. This 1D MPS structure was initially observed in axons and exists extensively in axons, spanning nearly the entire axonal shaft of mature neurons. Such 1D MPS was also observed in dendrites, but the extent to which it exists and how it develops in dendrites remain unclear. It is also unclear whether other structural forms of the membrane skeleton are present in neurons. Here, we investigated the spatial organizations of spectrin, actin, and adducin, an actin-capping protein, in the dendrites and soma of cultured hippocampal neurons at different developmental stages, and compared results with those obtained in axons, using superresolution imaging. We observed that the 1D MPS exists in a substantial fraction of dendritic regions in relatively mature neurons, but this structure develops slower and forms with a lower propensity in dendrites than in axons. In addition, we observed that spectrin, actin, and adducin also form a 2D polygonal lattice structure, resembling the expanded erythrocyte membrane skeleton structure, in the somatodendritic compartment. This 2D lattice structure also develops substantially more slowly in the soma and dendrites than the development of the 1D MPS in axons. These results suggest membrane skeleton structures are differentially regulated across different subcompartments of neurons.

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