Mapping Protein Networks in the Roundworm

Genome, transcriptome, proteome, and now we have the interactome, the full complement of protein-protein interactions that can occur in the cell. Marc Vidal and colleagues from the Dana-Farber Cancer Institute, Boston, and numerous other research centers, report in today's Sciencexpress the mapping of a substantial part of the C. elegans interactome network.

Interactomes get us closer to the business end of cell biology, but elucidating all the interactions among thousands of proteins is a Herculean task, as evident by the 10 first authors that cooperated to make this work happen. Together, Siming Li and colleagues identified more than 4,000 interactions using just over 3,000 protein "baits" in yeast two-hybrid screens.

The data Li and colleagues collected allowed them to describe highly connected networks of proteins that are likely to function in common cellular processes. As an example, the authors chose to feature two proteins, C49A1.4 and VAB-3, which are orthologs of the Eyes Absent and Eyeless transcription factors that regulate eye development in Drosophila. Li and colleagues found that the two C. elegans proteins, which share many binding partners, interact with eight proteins that are predicted to be involved in membrane function. These novel interactions suggest that membrane biology may play a role in regulating eye development.

These types of study, exemplified previously by the recent work of John Chant and colleagues who mapped over 7,000 interactions in Drosophila (see ARF related news story), represent the potential of "interactomics" to uncover novel protein partnerships that may help researchers understand pathogenesis and perhaps identify therapeutic targets.—Tom Fagan

Comments

  1. Although this paper represents a tremendous amount of work, it is not as strong a study as the similar one conduced recently in the fruit fly (Giot et al., 2003). Li et al. used only about one-fifth the number of bait targets as used in the fly work, so their interaction map is presumably less extensive than that constructed for the fly. Of more concern is the authors' own estimation that they have recapitulated only 10 percent of the already known interactions in their test set. The authors also make some comparisons between their data and the published C. elegans microarray data that don't seem compelling, although it is unclear if this indicates weaknesses in the data or a general lack of (biological) concurrence between protein interaction and transcriptional profiles.

    The real question is whether the high-throughput protein interaction datasets are really useful for understanding disease-associated protein function and pathology. In a simple test, I looked for interactions found for the fly and worm homologues of APP; apparently, none were identified in the fly study, and one (questionable?) interaction was found in C. elegans. This is obviously a limited sample test, and I am certain there will be instances where insights will be gained from these interactome maps. However, I think these insights may occur more commonly for disease genes that aren't already well-studied.

    References:

    Giot L, Bader JS, Brouwer C, Chaudhuri A, Kuang B, Li Y, Hao YL, Ooi CE, Godwin B, Vitols E, Vijayadamodar G, Pochart P, Machineni H, Welsh M, Kong Y, Zerhusen B, Malcolm R, Varrone Z, Collis A, Minto M, Burgess S, McDaniel L, Stimpson E, Spriggs F, Williams J, Neurath K, Ioime N, Agee M, Voss E, Furtak K, Renzulli R, Aanensen N, Carrolla S, Bickelhaupt E, Lazovatsky Y, DaSilva A, Zhong J, Stanyon CA, Finley RL, White KP, Braverman M, Jarvie T, Gold S, Leach M, Knight J, Shimkets RA, McKenna MP, Chant J, Rothberg JM. A protein interaction map of Drosophila melanogaster. Science. 2003 Dec 5;302(5651):1727-36. PubMed.

    View all comments by Chris Link

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References

News Citations

  1. Mapping Interactions in the Drosophila Proteome

Further Reading

Primary Papers

  1. Li S, Armstrong CM, Bertin N, Ge H, Milstein S, Boxem M, Vidalain PO, Han JD, Chesneau A, Hao T, Goldberg DS, Li N, Martinez M, Rual JF, Lamesch P, Xu L, Tewari M, Wong SL, Zhang LV, Berriz GF, Jacotot L, Vaglio P, Reboul J, Hirozane-Kishikawa T, Li Q, Gabel HW, Elewa A, Baumgartner B, Rose DJ, Yu H, Bosak S, Sequerra R, Fraser A, Mango SE, Saxton WM, Strome S, Van Den Heuvel S, Piano F, Vandenhaute J, Sardet C, Gerstein M, Doucette-Stamm L, Gunsalus KC, Harper JW, Cusick ME, Roth FP, Hill DE, Vidal M. A map of the interactome network of the metazoan C. elegans. Science. 2004 Jan 23;303(5657):540-3. PubMed.

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