| Title: |
Comparative analysis of ESCRT-I, ESCRT-II and ESCRT-III function in Drosophila by efficient isolation of ESCRT mutants |
| Authors: |
T. Vaccari; T. E. Rusten; L. Menut; I. P. Nezis; A. Brech; H. Stenmark; D. Bilder |
| Contributors: |
T. Vaccari; T.E. Rusten; L. Menut; I.P. Nezi; A. Brech; H. Stenmark; D. Bilder |
| Publisher Information: |
The Company of Biologists |
| Publication Year: |
2009 |
| Collection: |
The University of Milan: Archivio Istituzionale della Ricerca (AIR) |
| Subject Terms: |
Drosophila; Endocytosi; ESCRT; MVB sorting; Tumor suppression gene; Actin; Animal; Cell Proliferation; Cytoskeleton; Drosophila Protein; Endosomal Sorting Complexes Required for Transport; Endosome; Female; Genotype; Male; Phenotype; Phosphoprotein; Protein Processing; Post-Translational; Protein Stability; Protein Transport; Receptors; Notch; Ubiquitination; Vesicular Transport Protein; Mutation; Cell Biology; Settore BIO/13 - Biologia Applicata |
| Description: |
ESCRT proteins were initially isolated in yeast as a single functional set of conserved components controlling endosomal cargo sorting and multivesicular body (MVB) biogenesis. Recent work has suggested that metazoan ESCRT proteins might have more functionally diverse roles, but the limited availability of ESCRT mutants in species other than yeast has hampered a thorough analysis. Here, we used a genetic screening strategy based on both cell-autonomous and non-autonomous growthpromotion phenotypes to isolate null mutations in nearly half of the ESCRT-encoding genes of Drosophila, including components of ESCRT-I, ESCRT-II and ESCRT-III complexes. All ESCRT components are required for trafficking of ubiquitylated proteins and are required to prevent excess Notch and EGFR signaling. However, cells lacking certain ESCRT-III components accumulate fewer ubiquitylated molecules in endosomes and display reduced degrees of cell proliferation compared with those lacking components of ESCRT-I and ESCRT-II. Moreover, although we find by ultrastructural analysis that MVB formation is impaired in ESCRT-I and ESCRT-II mutant cells, MVB biogenesis still occurs to some degree in ESCRT-III mutant cells. This work highlights the multiple cell biological and developmental roles of ESCRT proteins in Drosophila, suggests that the metazoan ESCRT-I, ESCRT-II and ESCRT-III complexes do not serve identical functions, and provides the basis for an extensive analysis of metazoan ESCRT function. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
info:eu-repo/semantics/altIdentifier/pmid/19571114; info:eu-repo/semantics/altIdentifier/wos/WOS:000268257600010; volume:122; issue:14; firstpage:2413; lastpage:2423; numberofpages:11; journal:JOURNAL OF CELL SCIENCE; https://hdl.handle.net/2434/493179 |
| DOI: |
10.1242/jcs.046391 |
| Availability: |
https://hdl.handle.net/2434/493179; https://doi.org/10.1242/jcs.046391 |
| Rights: |
info:eu-repo/semantics/openAccess |
| Accession Number: |
edsbas.A6D96EA1 |
| Database: |
BASE |