title: Two Paralogous Tetraspanins TSP-12 and TSP-14 Function with the ADAM10 Metalloprotease SUP-17 to Promote BMP Signaling in Caenorhabditis elegans.
abstract: The highly conserved bone morphogenetic protein (BMP) signaling pathway regulates many developmental and homeostatic processes. While the core components of the BMP pathway have been well studied, much research is needed for understanding the mechanisms involved in the precise spatiotemporal control of BMP signaling in vivo. Here, we provide evidence that two paralogous and evolutionarily conserved tetraspanins, TSP-12 and TSP-14, function redundantly to promote BMP signaling in C. elegans. We further show that the ADAM10 (a disintegrin and metalloprotease 10) ortholog SUP-17 also functions to promote BMP signaling, and that TSP-12 can bind to and promote the cell surface localization of SUP-17. SUP-17/ADAM10 is known to be involved in the ligand-induced proteolytic processing of the Notch receptor. We have evidence that the function of SUP-17, and of TSP-12/TSP-14 in BMP signaling is independent of their roles in Notch signaling. Furthermore, presenilins, core components of the γ-secretase complex involved in processing Notch, do not appear to play a role in BMP signaling. These studies established a new role of the TSP-12/TSP-14/SUP-17 axis in regulating BMP signaling, in addition to their known function in the Notch signaling pathway. We also provide genetic evidence showing that a known BMP signaling modulator, UNC-40/neogenin/DCC, is one of the substrates of SUP-17/ADAM10 in the BMP signaling pathway.
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Lin
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Zhiyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Herong
authors.initials: H
authors.lastname: Shi
authors.affiliation: Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, United States of America.
authors.forename: Jun
authors.identifier: 0000-0001-7815-4075
authors.initials: J
authors.lastname: Liu
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D021381:Protein Transport; D015398:Signal Transduction; D059470:Tetraspanins / Q000235:genetics / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D029742:Caenorhabditis elegans Proteins; D008565:Membrane Proteins; C000619332:TSP-12 protein, C elegans; C000619333:TSP-14 protein, C elegans; D059470:Tetraspanins; C091279:neogenin; D008666:Metalloendopeptidases; C109978:SUP-17 protein, C elegans