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Vol. 19, Issue 12, 5409-5421, December 2008

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The Protein Interaction Network of the Epithelial Junctional Complex: A System-Level Analysis

Istituto di Ricerche Farmacologiche Mario Negri, I-20156 Milan, Italy

Submitted May 13, 2008; Revised September 25, 2008; Accepted October 2, 2008
Monitoring Editor: Asma Nusrat

To acquire system-level understanding of the intercellular junctional complex, protein–protein interactions occurring at the junctions of simple epithelial cells have been examined by network analysis. Although proper hubs (i.e., very rare proteins with exceedingly high connectivity) were absent from the junctional network, the most connected (albeit nonhub) proteins displayed a significant association with essential genes and contributed to the "small world" properties of the network (as shown by in vivo and in silico deletion, respectively). In addition, compared with a random network, the junctional network had greater tendency to form modules and subnets of densely interconnected proteins. Module analysis highlighted general organizing principles of the junctional complex. In particular, two major modules (corresponding to the tight junctions and to the adherens junctions/desmosomes) were linked preferentially to two other modules that acted as structural and signaling platforms.

Address correspondence to: Gianfranco Bazzoni (bazzoni{at}marionegri.it).

Abbreviations used: AJ, adherens junction; BC, betweenness centrality; C, clustering coefficient; DE, desmosome; k, degree of connectivity; JC, junctional complex; PPI, protein–protein interaction; TJ, tight junction.