Proteomic and functional analyses of the periodic membrane skeleton in neurons

Actin, spectrin, and associated proteins form a membrane-associated periodic skeleton (MPS) in neurons. The molecular composition and functions of the MPS remain incompletely understood. Here, we combined co-immunoprecipitation and mass spectrometry analyses to identify candidate MPS-interacting proteins from cultured hippocampal neurons and adult mouse brains. In addition, we also used quantitative mass spectrometry analysis based on Tandem Mass Tag (TMT) isobaric labeling to determine how the expression levels of proteins are differentially regulated at the proteomic scale upon depletion of βII-spectrin, an important molecular component of the MPS. These results provide a systematic picture of the interactome of the MPS, and new insights into new functions of the MPS in neurons.