Common and distinct genetic properties of ESCRT-II components in Drosophila.
BACKGROUND
Genetic studies in yeast have identified class E vps genes that form the ESCRT complexes required for protein sorting at the early endosome. In Drosophila, mutations of the ESCRT-II component vps25 cause endosomal defects leading to accumulation of Notch protein and increased Notch pathway activity. These endosomal and signaling defects are thought to account for several phenotypes. Depending on the developmental context, two different types of overgrowth can be detected. Tissue predominantly mutant for vps25 displays neoplastic tumor characteristics. In contrast, vps25 mutant clones in a wild-type background trigger hyperplastic overgrowth in a non-autonomous manner. In addition, vps25 mutant clones also promote apoptotic resistance in a non-autonomous manner.


RESULTS
Here, we genetically characterize the remaining ESCRT-II components vps22 and vps36. Like vps25, mutants of vps22 and vps36 display endosomal defects, accumulate Notch protein and--when the tissue is predominantly mutant--show neoplastic tumor characteristics. However, despite these common phenotypes, they have distinct non-autonomous phenotypes. While vps22 mutations cause strong non-autonomous overgrowth, they do not affect apoptotic resistance. In contrast, vps36 mutations increase apoptotic resistance, but have little effect on non-autonomous proliferation. Further characterization reveals that although all ESCRT-II mutants accumulate Notch protein, only vps22 and vps25 mutations trigger Notch activity.


CONCLUSIONS
The ESCRT-II components vps22, vps25 and vps36 display common and distinct genetic properties. Our data redefine the role of Notch for hyperplastic and neoplastic overgrowth in these mutants. While Notch is required for hyperplastic growth, it appears to be dispensable for neoplastic transformation.
Herz
Hans-Martin
HM
Department of Biochemistry and Molecular Biology, The Genes & Development Graduate Program, The University of Texas MD Anderson Cancer Center, Houston, Texas, United States of America.
Woodfield
Sarah E
SE
Chen
Zhihong
Z
Bolduc
Clare
C
Bergmann
Andreas
A
D000818:Animals; D017209:Apoptosis; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D056827:Endosomal Sorting Complexes Required for Transport; D011992:Endosomes / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010641:Phenotype; D021381:Protein Transport / Q000235:genetics; D051880:Receptors, Notch / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000235:genetics; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism
D002352:Carrier Proteins; D029721:Drosophila Proteins; D056827:Endosomal Sorting Complexes Required for Transport; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D033921:Vesicular Transport Proteins; C511665:Vps25 protein, Drosophila; C535102:Vps36 protein, Drosophila; C064045:delta protein; C535101:lsn protein, Drosophila