- THIS ARTICLE
- Full Text
- Full Text (PDF)
-
All Versions of this Article:
genetics.104.035170v1
172/4/2309 most recent - Alert me when this article is cited
- Alert me if a correction is posted
- SERVICES
- Email this article to a friend
- Similar articles in this journal
- Similar articles in PubMed
- Alert me to new issues of the journal
- Download to citation manager
- Reprints & Permissions
- CITING ARTICLES
- Citing Articles via HighWire
- Citing Articles via Google Scholar
- GOOGLE SCHOLAR
- Articles by Mahoney, M. B.
- Articles by Curtis, D.
- Search for Related Content
- PUBMED
- PubMed Citation
- Articles by Mahoney, M. B.
- Articles by Curtis, D.
Originally published as Genetics Published Articles Ahead of Print on January 16, 2006.
Genetics, Vol. 172, 2309-2324, April 2006, Copyright © 2006
doi:10.1534/genetics.104.035170
Presenilin-Based Genetic Screens in Drosophila melanogaster Identify Novel Notch Pathway Modifiers
Matt B. Mahoney1,2, Annette L. Parks1,3, David A. Ruddy1,4, Stanley Y. K. Tiong1, Hanife Esengil5, Alexander C. Phan6, Panos Philandrinos7, Christopher G. Winter8, Runa Chatterjee, Kari Huppert9, William W. Fisher10, Lynn L'Archeveque11, Felipa A. Mapa12, Wendy Woo, Michael C. Ellis13 and Daniel Curtis12
Exelixis, South San Francisco, California 94083
3 Corresponding author: Biology Department, Boston College, 140 Commonwealth Ave., Chestnut Hill, MA 02467.
E-mail: annette.parks.1{at}bc.edu
Presenilin is the enzymatic component of 
-secretase, a multisubunit intramembrane protease that processes several transmembrane receptors, such as the amyloid precursor protein (APP). Mutations in human Presenilins lead to altered APP cleavage and early-onset Alzheimer's disease. Presenilins also play an essential role in Notch receptor cleavage and signaling. The Notch pathway is a highly conserved signaling pathway that functions during the development of multicellular organisms, including vertebrates, Drosophila, and C. elegans. Recent studies have shown that Notch signaling is sensitive to perturbations in subcellular trafficking, although the specific mechanisms are largely unknown. To identify genes that regulate Notch pathway function, we have performed two genetic screens in Drosophila for modifiers of Presenilin-dependent Notch phenotypes. We describe here the cloning and identification of 19 modifiers, including nicastrin and several genes with previously undescribed involvement in Notch biology. The predicted functions of these newly identified genes are consistent with extracellular matrix and vesicular trafficking mechanisms in Presenilin and Notch pathway regulation and suggest a novel role for -tubulin in the pathway.
This article has been cited by other articles:
 |
|
 |
|
  M. Vazquez, M. T. Cooper, M. Zurita, and J. A. Kennison {gamma}Tub23C Interacts Genetically With Brahma Chromatin-Remodeling Complexes in Drosophila melanogaster Genetics, October 1, 2008; 180(2): 835 - 843. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Hayward, T. Kalmar, and A. Martinez Arias Wnt/Notch signalling and information processing during development Development, February 1, 2008; 135(3): 411 - 424. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Ganguly, R.M. R. Feldman, and M. Guo ubiquilin antagonizes presenilin and promotes neurodegeneration in Drosophila Hum. Mol. Genet., January 15, 2008; 17(2): 293 - 302. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. W. Kankel, G. D. Hurlbut, G. Upadhyay, V. Yajnik, B. Yedvobnick, and S. Artavanis-Tsakonas Investigating the Genetic Circuitry of Mastermind in Drosophila, a Notch Signal Effector Genetics, December 1, 2007; 177(4): 2493 - 2505. [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]
|
|