Article
- The EMBO Journal (2008) 27, 394 - 405
- doi:10.1038/sj.emboj.7601966
Published online: 10 January 2008
Subject Category:
SAGA-mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system
Vikki M Weake1, Kenneth K Lee1, Sebastián Guelman1,2, Chia-Hui Lin1, Christopher Seidel1, Susan M Abmayr1 and Jerry L Workman1
- Stowers Institute for Medical Research, Kansas City, MO, USA
Correspondence to:
Jerry L Workman, Stowers Institute for Medical Research, 1000 E 50th Street, Kansas City, MO 64110, USA. Tel.: +1 816 926 4392; Fax: +1 816 926 4692; E-mail: jlw@stowers-institute.org
2Present address: Genentech Inc., 1 DNA Way, South San Francisco, CA 94080-4990, USA
Received 14 June 2007; Accepted 30 November 2007
Abstract
Nonstop, which has previously been shown to have homology to ubiquitin proteases, is required for proper termination of axons R1–R6 in the optic lobe of the developing Drosophila eye. Herein, we establish that Nonstop actually functions as an ubiquitin protease to control the levels of ubiquitinated histone H2B in flies. We further establish that Nonstop is the functional homolog of yeast Ubp8, and can substitute for Ubp8 function in yeast cells. In yeast, Ubp8 activity requires Sgf11. We show that in Drosophila, loss of Sgf11 function causes similar photoreceptor axon-targeting defects as loss of Nonstop. Ubp8 and Sgf11 are components of the yeast SAGA complex, suggesting that Nonstop function might be mediated through the Drosophila SAGA complex. Indeed, we find that Nonstop does associate with SAGA components in flies, and mutants in other SAGA subunits display nonstop phenotypes, indicating that SAGA complex is required for accurate axon guidance in the optic lobe. Candidate genes regulated by SAGA that may be required for correct axon targeting were identified by microarray analysis of gene expression in SAGA mutants.
Keywords:
- H2B deubiquitination,
- histone acetyltransferase,
- neural development,
- Nonstop,
- SAGA
