SAGA-mediated H2B deubiquitination controls the development of neuronal connectivity in the Drosophila visual system.
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.
Weake
Vikki M
VM
Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
Lee
Kenneth K
KK
Guelman
Sebastián
S
Lin
Chia-Hui
CH
Seidel
Christopher
C
Abmayr
Susan M
SM
Workman
Jerry L
JL
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000235:genetics / Q000378:metabolism*; D010450:Endopeptidases / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009154:Mutation; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009899:Optic Lobe, Nonmammalian / Q000254:growth & development / Q000378:metabolism; D010802:Phylogeny; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D054875:Ubiquitination; D000099224:p300-CBP-Associated Factor
D029721:Drosophila Proteins; D010450:Endopeptidases; D051548:Histone Acetyltransferases; D006657:Histones; C470558:Ada2a protein, Drosophila; C470557:GCN5 protein, Drosophila; D000099224:p300-CBP-Associated Factor; C421164:not protein, Drosophila