In silico modeling and analyses of the protein-protein interaction network of the actin/spectrin membrane-associated periodic skeleton of axons: Topological features of the network predicts functional segmentation of its components

BRUNO G; GAZAL NG; RAMOS FO; SOSA JM; ZAMPONI N; UNSAIN N

Santa Cruz

Congreso; IUBMB EMBO Workshop Emerging Concepts of the Neuronal Cytoskeleton. Santa Cruz, Chile; 2023

EMBO

The actin/spectrin membrane-associated periodic skeleton (MPS) is a periodic protein structureconsisting of actin "rings" located transversely to the axon and separated every 190 nm by α/β-spectrintetramers "spacers". In mature neurons, the MPS is present along almost the entire axonal axis.Despite being evolutionarily conserved, little is known about the functions of this structure. In thepresent work, we predicted the protein-protein interaction network (or the interactome) of the axonalMPS from public databases. To determine the mesoscale functional organization of the MPSinteractome, we identified topological modules in the axonal interactone and performed a GeneOntology enrichment analysis of the modules in which the MPS core proteins were located.Interestingly, we found that the core components of the MPS are located in many different modules thatare enriched in different functional categories. For example, module 3, where the α/β-spectrin islocated, is enriched in small GTPase signaling and protein phosphorylation, while module 27, where theα-adducin is located, is enriched in positive regulation of fatty acid transport and organic hydroxycompound biosynthetic process. In addition, we predicted the MPS axonal interactome fromphylogenetically distant organisms and found that this network is conserved both at the level ofcomponents and interactions. Our analyses provide new insights into the structure and organization ofthe axonal MPS.