Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states
The Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we an...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2014-09-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/02950 |
| _version_ | 1811253300928970752 |
|---|---|
| author | Lauren LeBon Tom V Lee David Sprinzak Hamed Jafar-Nejad Michael B Elowitz |
| author_facet | Lauren LeBon Tom V Lee David Sprinzak Hamed Jafar-Nejad Michael B Elowitz |
| author_sort | Lauren LeBon |
| collection | DOAJ |
| description | The Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we analyzed same-cell (cis) Notch-ligand interactions for Notch1, Dll1, and Jag1, and their dependence on Fringe protein expression in mammalian cells. We found that Dll1 and Jag1 can cis-inhibit Notch1, and Fringe proteins modulate these interactions in a way that parallels their effects on trans interactions. Fringe similarly modulated Notch-ligand cis interactions during Drosophila development. Based on these and previously identified interactions, we show how the design of the Notch signaling pathway leads to a restricted repertoire of signaling states that promote heterotypic signaling between distinct cell types, providing insight into the design principles of the Notch signaling system, and the specific developmental process of Drosophila dorsal-ventral boundary formation. |
| first_indexed | 2024-04-12T16:48:49Z |
| format | Article |
| id | doaj.art-44f737d56ed8479c9124b2651908442d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-12T16:48:49Z |
| publishDate | 2014-09-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-44f737d56ed8479c9124b2651908442d2022-12-22T03:24:28ZengeLife Sciences Publications LtdeLife2050-084X2014-09-01310.7554/eLife.02950Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling statesLauren LeBon0Tom V Lee1David Sprinzak2Hamed Jafar-Nejad3Michael B Elowitz4Howard Hughes Medical Institute, California Institute of Technology, Pasadena, United States; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesDepartment of Biochemistry and Molecular Biology, Tel Aviv University, Tel Aviv, IsraelDepartment of Molecular and Human Genetics, Baylor College of Medicine, Houston, United StatesHoward Hughes Medical Institute, California Institute of Technology, Pasadena, United States; Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United StatesThe Notch signaling pathway consists of multiple types of receptors and ligands, whose interactions can be tuned by Fringe glycosyltransferases. A major challenge is to determine how these components control the specificity and directionality of Notch signaling in developmental contexts. Here, we analyzed same-cell (cis) Notch-ligand interactions for Notch1, Dll1, and Jag1, and their dependence on Fringe protein expression in mammalian cells. We found that Dll1 and Jag1 can cis-inhibit Notch1, and Fringe proteins modulate these interactions in a way that parallels their effects on trans interactions. Fringe similarly modulated Notch-ligand cis interactions during Drosophila development. Based on these and previously identified interactions, we show how the design of the Notch signaling pathway leads to a restricted repertoire of signaling states that promote heterotypic signaling between distinct cell types, providing insight into the design principles of the Notch signaling system, and the specific developmental process of Drosophila dorsal-ventral boundary formation.https://elifesciences.org/articles/02950cell signalingdevelopmental patterningnotch pathwaysystems biology |
| spellingShingle | Lauren LeBon Tom V Lee David Sprinzak Hamed Jafar-Nejad Michael B Elowitz Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states eLife cell signaling developmental patterning notch pathway systems biology |
| title | Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states |
| title_full | Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states |
| title_fullStr | Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states |
| title_full_unstemmed | Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states |
| title_short | Fringe proteins modulate Notch-ligand cis and trans interactions to specify signaling states |
| title_sort | fringe proteins modulate notch ligand cis and trans interactions to specify signaling states |
| topic | cell signaling developmental patterning notch pathway systems biology |
| url | https://elifesciences.org/articles/02950 |
| work_keys_str_mv | AT laurenlebon fringeproteinsmodulatenotchligandcisandtransinteractionstospecifysignalingstates AT tomvlee fringeproteinsmodulatenotchligandcisandtransinteractionstospecifysignalingstates AT davidsprinzak fringeproteinsmodulatenotchligandcisandtransinteractionstospecifysignalingstates AT hamedjafarnejad fringeproteinsmodulatenotchligandcisandtransinteractionstospecifysignalingstates AT michaelbelowitz fringeproteinsmodulatenotchligandcisandtransinteractionstospecifysignalingstates |