Little is known about the molecular mechanisms underlying alveolar development. P311, a putative neuronal protein originally identified for its high expression during neuronal development, has once been reported to play a potential role in distal lung generation. However, the function of this protein has been poorly understood so far. Hence, we carried out a yeast two-hybrid screen, combining with other protein-protein interaction experiments, to isolate several binding partners of P311 during lung development, which may help us explore its function. We report 7 proteins here, including Gal-1, Loxl-1 and SPARC, etc, that can interact with it. Most of them have similar spatio-temporal expression patterns to P311. In addition, it was also found that P311 could stimulate their expression indirectly in L929 mouse fibroblast. Besides, computational methods were applied to construct a P311 centered protein-protein interaction network during alveolarization, using the 7 binding partners and their protein interaction information provided by public data resources. By analyzing the structure and function of this network, the effects of P311 on lung development were further clarified and all of the bioinformatic predictions from the network could be validated by real experiments. We have found here that P311 can control lung redox events, extracellular matrix and cell cycle progression, which are all crucial to pulmonary morphogenesis. This gives us a novel thought to explore the mechanisms controlling alveolarization.
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