Source: http://cegg.unige.ch/insecta/immunodb

APHAGs: Autophagy Genes
Summary

Bart Bryant(1) and Lyric Bartholomay(2) 

1. Division of Biology, Kansas State University, Rollie Clem Lab, Ackert Hall, Manhattan, KS 66506-4901 
2. Department of Entomology, 442 Science Hall 2, Iowa State University, Ames IA 50011-3222 

Autophagy is a form of cell death characterized by the formation of an internal double membrane-delimited vacuole called an autophagosome. Within the autophagosome, internalized pathogens are degraded. This process is critical for recycling cellular contents during starvation events, such that homeostasis is maintained. Autophagy also functions in innate and adaptive immunity to protect organisms from intracellular pathogens. 

Genes involved in autophagy are designated autophagy related genes (Atg), and are numbered successively. Atg proteins are involved in signal transduction cascades that result in the formation of the autophagosome. The process of autophagy can be subdivided into three phases: regulation of induction (TOR1, Atg1, Atg13), vesicle nucleation (Atg6, Vps34, Vps15, Bcl-2 (buffy in Drosophila), vesicle expansion (Atg3, Atg4, Atg5, Atg7, Atg8, Atg10, Atg12, and Atg16) and recycling (Atg2, Atg9, Atg18) (Melendez A and Neufeld TP. Development. 2008, [review of Drosophila autophagy genes] Baehrecke EH. Cell Death and Differentiation. 2003). Therefore, although autophagy genes share a common nomenclature, their functions are diverse. For example Atg1 has a S/T kinase domain followed by a microtubule interacting and trafficking domain followed by a transmembrane domain. Other Atg genes do not have this domain architecture (i.e. Atg4 has a C54 peptidase domain). 

The Atg genes are extremely homologous among the dipterans analyzed here (Drosophila melanogaster, Anopheles gambiae, Aedes aegypti, and Culex quinquefasciatus). Interestingly, these genes do not exhibit significant duplication as compared to other cell death gene families represented in ImmunoDB (i.e. caspases and IAPs), which suggests these genes are highly constrained by evolutionary pressures. There are only a few duplications we observed in mosquitoes compared to Drosophila melanogaster. These genes are Atg4, and Atg18. In other systems, Atg4 has been shown to be involved in vesicle expansion and Atg18 has been shown to be involved in recycling. Duplications in these genes could reflect alternate regulation of vesicle expansion and recycling in mosquitoes, or these might be pseudogenes. 

Bcl-2-like genes were also included in the autophagy group due to recently demonstrated overlap of apoptosis and autophagy in mammalian studies (Levine B et al. [Review] Autophagy. 2008). Initially these types of proteins have been shown to be involved in regulating cytochrome c release from the mitochondria. This release is known to play a part in the activation of the apoptosome. Additionally, Bcl-2 has been shown to inhibit Beclin-1 (Atg6) from interacting with Vps34 (Levine B et al. [Review] Autophagy. 2008). Protein sequences identified in Drosophila were used to search the three mosquito genomes for autophagy-related genes. In Drosophila, only two Bcl-like proteins that have been studied; buffy (Quinn L et al. EMBO J. 2003) and Debcl (Colussi PA. J Cell Biol. 2000), and there has been controversy over what roles (pro- or anti-apoptotic) these genes play in regulating apoptosis. In all mosquitoes analyzed there are homologues for both of these genes. 

Neufeld & Baehrecke, 2008, Autophagy PMID:18319640 
Eating on the fly: function and regulation of autophagy during cell growth, survival and death in Drosophila.