A Systemic Model for the Receptor Complex NRC/MASC Based On Its Inferred Interproteic Network

The main glutamate receptor complex NRC/MASC (NMDA receptor complex/ MAGUK associated signalling complex) has been identified as the key element for glutamate reception process and the modulation of the signal delivered by the neurotransmitter. Interproteic interactions have been used to model and identify the main functional modules and signalling pathways related to this cognitive illnesses. In this work we present a novel approach for modeling and analysing protein complexes such as the NRC/MASC complex. Our methodology generates a consensus network of interproteic interactions integrating a probabilistic network inferred by Naïve-Bayes classifier, with other networks previously reported in literature. Functional modules in the network were identified by a clustering algorithm, into twelve highly specialised modules, some of which have not been reported previously. These modules were used to gain insight into underlying mechanisms behind synaptic plasticity and cognitive diseases. A new organisational structure for the NRC/MASC arose from the analysis of the characteristics of the components of these modules. Proteins altered in cognitive diseases are grouped into distinctive modules. A new functional structure for the receptor unit NRC/MASC is proposed, whose composition and organisation comprises inferred probabilistic protein interactions and experimentally documented interactions previously reported. This structure with highly specialised modules is a comprehensive tool to study the complex mechanisms behind diseases like schizophrenia and mental retardation. The methodology presented can be applied for the inference of interproteic interactions and network structures in other protein networks of interest.

This work was partially supported by FONDECYT Research Initiation Grant 11080016.