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Letter
Aph-1 is required to regulate Presenilin-mediated γ-secretase activity and cell survival in Drosophila wing development
Article first published online: 3 FEB 2009
DOI: 10.1002/dvg.20478
Copyright © 2009 Wiley-Liss, Inc.
Additional Information
How to Cite
Cooper, E., Deng, W.-M. and Chung, H.-M. (2009), Aph-1 is required to regulate Presenilin-mediated γ-secretase activity and cell survival in Drosophila wing development. Genesis, 47: 169–174. doi: 10.1002/dvg.20478
Publication History
- Issue published online: 23 MAR 2009
- Article first published online: 3 FEB 2009
- Manuscript Accepted: 25 OCT 2008
- Manuscript Revised: 19 OCT 2008
- Manuscript Received: 8 SEP 2008
Funded by
- NIH. Grant Number: 1R15AG028448-01
- University of West Florida
- Abstract
- References
- Cited By
Keywords:
- Presenilin;
- Aph-1;
- γ-secretase;
- Notch;
- cell survival
Abstract
Aph-1 is a multipass transmembrane protein and an essential component of the Presenilin (Psn)-mediated γ-secretase complex. During protease assembly, Aph-1 stabilizes the newly synthesized Psn holoprotein to facilitate generation of the active form of Psn, which is a Psn-NTF/Psn-CTF heterodimer produced through a Presenilinase-initiated endoproteolytic cleavage of the Psn holoprotein. Although it is clear that loss of Aph-1 activity leads to failure of Psn heterodimer formation, little is understood about whether Aph-1 plays a role in regulating γ-secretase activity in addition to assisting Psn maturation. Using various modified Psn forms that do not require endoproteolysis or have a large deletion of the cytosolic loop, we show that in Drosophila Aph-1 is still required for γ-secretase activity independent of its role in promoting Psn endoproteolysis. In addition, our results indicate that Aph-1 is required to promote cell survival in the wing imaginal disc; aph-1 mutant cells are lost either through cell death or because of a defect in cell proliferation. This function of Aph-1 is independent of its role in regulating γ-secretase activity, but possibly involves downregulating the activity of uncleaved Psn holoprotein. genesis 47:169–174, 2009. © 2009 Wiley-Liss, Inc.