University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Cancer Biology

Date

3-15-2013

Document Type

Article

Medical Subject Headings

Animals; Animals, Genetically Modified; Autophagy; Biological Transport; Drosophila Proteins; *Drosophila melanogaster; Endosomal Sorting Complexes Required for Transport; Epistasis, Genetic; Hematopoiesis; Larva; Protein Transport; Secretory Pathway; Signal Transduction; Transport Vesicles; Vesicular Transport Proteins

Disciplines

Cancer Biology | Cell and Developmental Biology | Cell Biology

Abstract

Atg6 (beclin 1 in mammals) is a core component of the Vps34 complex that is required for autophagy. Beclin 1 (Becn1) functions as a tumor suppressor, and Becn1(+/-) tumors in mice possess elevated cell stress and p62 levels, altered NF-kappaB signaling and genome instability. The tumor suppressor function of Becn1 has been attributed to its role in autophagy, and the potential functions of Atg6/Becn1 in other vesicle trafficking pathways for tumor development have not been considered. Here, we generate Atg6 mutant Drosophila and demonstrate that Atg6 is essential for autophagy, endocytosis and protein secretion. By contrast, the core autophagy gene Atg1 is required for autophagy and protein secretion, but it is not required for endocytosis. Unlike null mutants of other core autophagy genes, all Atg6 mutant animals possess blood cell masses. Atg6 mutants have enlarged lymph glands (the hematopoietic organ in Drosophila), possess elevated blood cell numbers, and the formation of melanotic blood cell masses in these mutants is not suppressed by mutations in either p62 or NFkappaB genes. Thus, like mammals, altered Atg6 function in flies causes hematopoietic abnormalities and lethality, and our data indicate that this is due to defects in multiple membrane trafficking processes.

Rights and Permissions

Citation: Development. 2013 Mar;140(6):1321-9. doi: 10.1242/dev.089490. Epub 2013 Feb 13. Link to article on publisher's site

Comments

Publisher PDF posted as allowed by the publisher's author rights policy at http://dev.biologists.org/site/misc/rights_permissions.xhtml#author

Related Resources

Link to Article in PubMed

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