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An Extracellular Interactome of Immunoglobulin and LRR Proteins Reveals Receptor-Ligand Networks

Özkan, Engin and Carrillo, Robert A. and Eastman, Catharine L. and Weiszmann, Richard and Waghray, Deepa and Johnson, Karl G. and Zinn, Kai and Celniker, Susan E. and Garcia, K. Christopher (2013) An Extracellular Interactome of Immunoglobulin and LRR Proteins Reveals Receptor-Ligand Networks. Cell, 154 (1). pp. 228-239. ISSN 0092-8674. PMCID PMC3756661. doi:10.1016/j.cell.2013.06.006.

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Extracellular domains of cell surface receptors and ligands mediate cell-cell communication, adhesion, and initiation of signaling events, but most existing protein-protein “interactome” data sets lack information for extracellular interactions. We probed interactions between receptor extracellular domains, focusing on a set of 202 proteins composed of the Drosophila melanogaster immunoglobulin superfamily (IgSF), fibronectin type III (FnIII), and leucine-rich repeat (LRR) families, which are known to be important in neuronal and developmental functions. Out of 20,503 candidate protein pairs tested, we observed 106 interactions, 83 of which were previously unknown. We “deorphanized” the 20 member subfamily of defective-in-proboscis-response IgSF proteins, showing that they selectively interact with an 11 member subfamily of previously uncharacterized IgSF proteins. Both subfamilies interact with a single common “orphan” LRR protein. We also observed interactions between Hedgehog and EGFR pathway components. Several of these interactions could be visualized in live-dissected embryos, demonstrating that this approach can identify physiologically relevant receptor-ligand pairs.

Item Type:Article
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URLURL TypeDescription CentralArticle
Özkan, Engin0000-0002-0263-6729
Carrillo, Robert A.0000-0002-2067-9861
Zinn, Kai0000-0002-6706-5605
Garcia, K. Christopher0000-0001-9273-0278
Additional Information:© 2013 Elsevier Inc. Received: November 28, 2012. Revised: April 2, 2013. Accepted: June 5, 2013. Published: July 3, 2013. We would like to thank Natalia Goriatcheva for technical help; Kevin J. Mitchell and Karsten Hokamp for sharing their list of Drosophila melanogaster LRR proteins; Claudia Y. Janda for technical discussions on interaction assays; Stephen R. Quake, Liqun Luo, Xiaomeng M. Yu, Weizhe Hong, and Marena Tynan La Fontaine for discussions; Nick V. Grishin for discussions on bioinformatics; and Demet Arac¸ and Michael E. Birnbaum for critical reading of the manuscript. Work at Pomona, Caltech, and LBNL was supported by NSF grant 0841551 to K.G.J., by NIH RO1 grants NS62821 and NS28182 to K.Z., and by NHGRI grant P41HG3487 to S.E.C. through the Department of Energy under contract DE-AC02-05CH11231, respectively. K.C.G. is an Investigator of the Howard Hughes Medical Institute.
Funding AgencyGrant Number
NIHRO1 NS62821
NIHRO1 NS28182
Department of Energy (DOE)DE-AC02-05CH11231
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
Issue or Number:1
PubMed Central ID:PMC3756661
Record Number:CaltechAUTHORS:20130813-154634927
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Official Citation:Engin Özkan, Robert A. Carrillo, Catharine L. Eastman, Richard Weiszmann, Deepa Waghray, Karl G. Johnson, Kai Zinn, Susan E. Celniker, K. Christopher Garcia, An Extracellular Interactome of Immunoglobulin and LRR Proteins Reveals Receptor-Ligand Networks, Cell, Volume 154, Issue 1, 3 July 2013, Pages 228-239, ISSN 0092-8674, (
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39904
Deposited By: Ruth Sustaita
Deposited On:14 Aug 2013 16:27
Last Modified:09 Nov 2021 23:47

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