spacer gif spacer gif spacer gif spacer gif ARCHIVE ANNOUNCEMENT! spacer gif
QUICK SEARCH:   [advanced]


spacer gif
     Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents    

First published online 19 October 2005
doi: 10.1242/dev.02076

Development 132, 5081-5092 (2005)
Published by The Company of Biologists 2005
This Article
Right arrow Figures Only
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
dev.02076v1
132/22/5081    most recent
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Shaye, D. D.
Right arrow Articles by Greenwald, I.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Shaye, D. D.
Right arrow Articles by Greenwald, I.

LIN-12/Notch trafficking and regulation of DSL ligand activity during vulval induction in Caenorhabditis elegans

Daniel D. Shaye1,2,* and Iva Greenwald1,3,{dagger}

1 Howard Hughes Medical Institute, Columbia University, New York, NY 10032, USA
2 Department of Genetics and Development, Columbia University, New York, NY 10032, USA
3 Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY 10032, USA

{dagger} Author for correspondence (e-mail: greenwald{at}cancercenter.columbia.edu)

Accepted 5 September 2005

A novel mode of crosstalk between the EGFR-Ras-MAPK and LIN-12/Notch pathways occurs during the patterning of a row of vulval precursor cells (VPCs) in Caenorhabditis elegans: activation of the EGFR-Ras-MAPK pathway in the central VPC promotes endocytosis and degradation of LIN-12 protein. LIN-12 downregulation in the central VPC is a prerequisite for the activity of the lateral signal, which activates LIN-12 in neighboring VPCs. Here we characterize cis-acting targeting sequences in the LIN-12 intracellular domain and find that in addition to a di-leucine motif, serine/threonine residues are important for internalization and lysine residues are important for post-internalization trafficking and degradation. We also identify two trans-acting factors that are required for post-internalization trafficking and degradation: ALX-1, a homolog of yeast Bro1p and mammalian Alix and the WWP-1/Su(dx)/Itch ubiquitin ligase. By examining the effects of mutated forms of LIN-12 and reduced wwp-1 or alx-1 activity on subcellular localization and activity of LIN-12, we provide evidence that the lateral signal-inhibiting activity of LIN-12 resides in the extracellular domain and occurs at the apical surface of the VPCs.

Key words: Notch, Ras, Endocytosis, C. elegans




This article has been cited by other articles:


Home page
 Genes Dev.Home page
A. V. Samuelson, C. E. Carr, and G. Ruvkun
Gene activities that mediate increased life span of C. elegans insulin-like signaling mutants
Genes & Dev., November 15, 2007; 21(22): 2976 - 2994.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M.-Y. Kim, E.-J. Ann, J.-Y. Kim, J.-S. Mo, J.-H. Park, S.-Y. Kim, M.-S. Seo, and H.-S. Park
Tip60 Histone Acetyltransferase Acts as a Negative Regulator of Notch1 Signaling by Means of Acetylation
Mol. Cell. Biol., September 15, 2007; 27(18): 6506 - 6519.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
Y. Liu and E. M. Maine
The Bro1-Domain Protein, EGO-2, Promotes Notch Signaling in Caenorhabditis elegans
Genetics, August 1, 2007; 176(4): 2265 - 2277.
[Abstract] [Full Text] [PDF]

Home page
 DevelopmentHome page
N. de Souza, L. G. Vallier, H. Fares, and I. Greenwald
SEL-2, the C. elegans neurobeachin/LRBA homolog, is a negative regulator of lin-12/Notch activity and affects endosomal traffic in polarized epithelial cells
Development, February 15, 2007; 134(4): 691 - 702.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
I. Katic and I. Greenwald
EMB-4: A Predicted ATPase That Facilitates lin-12 Activity in Caenorhabditis elegans
Genetics, December 1, 2006; 174(4): 1907 - 1915.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
M. Y. Chiang, M. L. Xu, G. Histen, O. Shestova, M. Roy, Y. Nam, S. C. Blacklow, D. B. Sacks, W. S. Pear, and J. C. Aster
Identification of a Conserved Negative Regulatory Sequence That Influences the Leukemogenic Activity of NOTCH1.
Mol. Cell. Biol., August 1, 2006; 26(16): 6261 - 6271.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
C. A. Giurumescu, P. W. Sternberg, and A. R. Asthagiri
Intercellular coupling amplifies fate segregation during Caenorhabditis elegans vulval development
PNAS, January 31, 2006; 103(5): 1331 - 1336.
[Abstract] [Full Text] [PDF]

Home page
 GeneticsHome page
I. Katic, L. G. Vallier, and I. Greenwald
New Positive Regulators of lin-12 Activity in Caenorhabditis elegans Include the BRE-5/Brainiac Glycosphingolipid Biosynthesis Enzyme
Genetics, December 1, 2005; 171(4): 1605 - 1615.
[Abstract] [Full Text] [PDF]

Home page
 ScienceHome page
A. S. Yoo and I. Greenwald
LIN-12/Notch Activation Leads to MicroRNA-Mediated Down-Regulation of Vav in C. elegans
Science, November 25, 2005; 310(5752): 1330 - 1333.
[Abstract] [Full Text] [PDF]


© The Company of Biologists Ltd 2005