|
|
|
|
|
|
|
||||
| Home Help Feedback Subscriptions Archive Search Table of Contents | ||||
First published online 6 October 2004
doi: 10.1242/dev.01434
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Section of Molecular Cell and Developmental Biology, Institute for Cellular and Molecular Biology, The University of Texas at Austin, Moffett Molecular Biology Building, 2500 Speedway, Austin, TX 78712, USA
* Author for correspondence (e-mail: jaf{at}mail.utexas.edu)
Accepted 8 September 2004
Endocytosis modulates the Notch signaling pathway in both the signaling and receiving cells. One recent hypothesis is that endocytosis of the ligand Delta by the signaling cells is essential for Notch activation in the receiving cells. Here, we present evidence in strong support of this model. We show that in the developing Drosophila eye Fat facets (Faf), a deubiquitinating enzyme, and its substrate Liquid facets (Lqf), an endocytic epsin, promote Delta internalization and Delta signaling in the signaling cells. We demonstrate that while Lqf is necessary for three different Notch/Delta signaling events at the morphogenetic furrow, Faf is essential only for one: Delta signaling by photoreceptor precluster cells, which prevents recruitment of ectopic neurons. In addition, we show that the ubiquitin-ligase Neuralized (Neur), which ubiquitinates Delta, functions in the signaling cells with Faf and Lqf. The results presented bolster one model for Neur function in which Neur enhances Delta signaling by stimulating Delta internalization in the signaling cells. We propose that Faf plays a role similar to that of Neur in the Delta signaling cells. By deubiquitinating Lqf, which enhances the efficiency of Delta internalization, Faf stimulates Delta signaling.
Key words: Eye, Drosophila, Notch, Delta, fat facets, liquid facets, Epsin, Endocytosis, Deubiquitinating enzyme, Ubiquitin
Related articles in Development:
This article has been cited by other articles:
|
|
 |
|
  S. H. Eun, S. M. L. Banks, and J. A. Fischer Auxilin is essential for Delta signaling Development, March 15, 2008; 135(6): 1089 - 1095. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. K. Bajpe, J. A. van der Knaap, J. A. A. Demmers, K. Bezstarosti, A. Bassett, H. M. M. van Beusekom, A. A. Travers, and C. P. Verrijzer Deubiquitylating Enzyme UBP64 Controls Cell Fate through Stabilization of the Transcriptional Repressor Tramtrack Mol. Cell. Biol., March 1, 2008; 28(5): 1606 - 1615. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Koutelou, S. Sato, C. Tomomori-Sato, L. Florens, S. K. Swanson, M. P. Washburn, M. Kokkinaki, R. C. Conaway, J. W. Conaway, and N. K. Moschonas Neuralized-like 1 (Neurl1) Targeted to the Plasma Membrane by N-Myristoylation Regulates the Notch Ligand Jagged1 J. Biol. Chem., February 15, 2008; 283(7): 3846 - 3853. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Roca and R. H. Adams Regulation of vascular morphogenesis by Notch signaling Genes & Dev., October 15, 2007; 21(20): 2511 - 2524. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E.-A. Choe, L. Liao, J.-Y. Zhou, D. Cheng, D. M. Duong, P. Jin, L.-H. Tsai, and J. Peng Neuronal Morphogenesis Is Regulated by the Interplay between Cyclin-Dependent Kinase 5 and the Ubiquitin Ligase Mind Bomb 1 J. Neurosci., August 29, 2007; 27(35): 9503 - 9512. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Eun, K. Lea, E. Overstreet, S. Stevens, J.-H. Lee, and J. A. Fischer Identification of Genes That Interact With Drosophila liquid facets Genetics, March 1, 2007; 175(3): 1163 - 1174. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Traub and G. L. Lukacs Decoding ubiquitin sorting signals for clathrin-dependent endocytosis by CLASPs J. Cell Sci., February 15, 2007; 120(4): 543 - 553. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Commisso and G. L. Boulianne The NHR1 Domain of Neuralized Binds Delta and Mediates Delta Trafficking and Notch Signaling Mol. Biol. Cell, January 1, 2007; 18(1): 1 - 13. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Mouchantaf, B. A. Azakir, P. S. McPherson, S. M. Millard, S. A. Wood, and A. Angers The Ubiquitin Ligase Itch Is Auto-ubiquitylated in Vivo and in Vitro but Is Protected from Degradation by Interacting with the Deubiquitylating Enzyme FAM/USP9X J. Biol. Chem., December 15, 2006; 281(50): 38738 - 38747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. L. Parks, J. R. Stout, S. B. Shepard, K. M. Klueg, A. A. Dos Santos, T. R. Parody, M. Vaskova, and M. A. T. Muskavitch Structure-Function Analysis of Delta Trafficking, Receptor Binding and Signaling in Drosophila Genetics, December 1, 2006; 174(4): 1947 - 1961. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Song, B.-K. Koo, K.-J. Yoon, M.-J. Yoon, K.-W. Yoo, H.-T. Kim, H.-J. Oh, Y.-Y. Kim, J.-K. Han, C.-H. Kim, et al. Neuralized-2 Regulates a Notch Ligand in Cooperation with Mind Bomb-1 J. Biol. Chem., November 24, 2006; 281(47): 36391 - 36400. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. M. Millard and S. A. Wood Riding the DUBway: regulation of protein trafficking by deubiquitylating enzymes J. Cell Biol., May 22, 2006; 173(4): 463 - 468. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Wang, L. M. Traub, K. M. Weixel, M. J. Hawryluk, N. Shah, R. S. Edinger, C. J. Perry, L. Kester, M. B. Butterworth, K. W. Peters, et al. Clathrin-mediated Endocytosis of the Epithelial Sodium Channel: ROLE OF EPSIN J. Biol. Chem., May 19, 2006; 281(20): 14129 - 14135. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. J. Hagedorn, J. L. Bayraktar, V. R. Kandachar, T. Bai, D. M. Englert, and H. C. Chang Drosophila melanogaster auxilin regulates the internalization of Delta to control activity of the Notch signaling pathway J. Cell Biol., May 8, 2006; 173(3): 443 - 452. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Pitsouli and C. Delidakis The interplay between DSL proteins and ubiquitin ligases in Notch signaling Development, September 15, 2005; 132(18): 4041 - 4050. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Roegiers, L. Y. Jan, and Y. N. Jan Regulation of Membrane Localization of Sanpodo by lethal giant larvae and neuralized in Asymmetrically Dividing Cells of Drosophila Sensory Organs Mol. Biol. Cell, August 1, 2005; 16(8): 3480 - 3487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Wang and G. Struhl Distinct roles for Mind bomb, Neuralized and Epsin in mediating DSL endocytosis and signaling in Drosophila Development, June 15, 2005; 132(12): 2883 - 2894. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. C. Lai, F. Roegiers, X. Qin, Y. N. Jan, and G. M. Rubin The ubiquitin ligase Drosophila Mind bomb promotes Notch signaling by regulating the localization and activity of Serrate and Delta Development, May 15, 2005; 132(10): 2319 - 2332. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Le Borgne, A. Bardin, and F. Schweisguth The roles of receptor and ligand endocytosis in regulating Notch signaling Development, April 15, 2005; 132(8): 1751 - 1762. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Chen and P. De Camilli From the Cover: The association of epsin with ubiquitinated cargo along the endocytic pathway is negatively regulated by its interaction with clathrin PNAS, February 22, 2005; 102(8): 2766 - 2771. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
X. Tian, D. Hansen, T. Schedl, and J. B. Skeath Epsin potentiates Notch pathway activity in Drosophila and C. elegans Development, December 1, 2004; 131(23): 5807 - 5815. [Abstract] [Full Text] [PDF]
|
|
