Genetic interactions between Drosophila melanogaster Atg1 and paxillin reveal a role for paxillin in autophagosome formation.
Autophagy is a conserved cellular process of macromolecule recycling that involves vesicle-mediated degradation of cytoplasmic components. Autophagy plays essential roles in normal cell homeostasis and development, the response to stresses such as nutrient starvation, and contributes to disease processes including cancer and neurodegeneration. Although many of the autophagy components identified from genetic screens in yeast are well conserved in higher organisms, the mechanisms by which this process is regulated in any species are just beginning to be elucidated. In a genetic screen in Drosophila melanogaster, we have identified a link between the focal adhesion protein paxillin and the Atg1 kinase, which has been previously implicated in autophagy. In mammalian cells, we find that paxillin is redistributed from focal adhesions during nutrient deprivation, and paxillin-deficient cells exhibit defects in autophagosome formation. Together, these findings reveal a novel evolutionarily conserved role for paxillin in autophagy.
Chen
Guang-Chao
GC
Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
Lee
Janice Y
JY
Tang
Hong-Wen
HW
Debnath
Jayanta
J
Thomas
Sheila M
SM
Settleman
Jeffrey
J
D000818:Animals; D030801:Animals, Genetically Modified; D017209:Apoptosis / Q000502:physiology; D001343:Autophagy / Q000502:physiology*; D000071189:Autophagy-Related Protein-1 Homolog; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000033:anatomy & histology / Q000235:genetics / Q000502:physiology*; D006706:Homeostasis; D016023:Integrins / Q000235:genetics / Q000378:metabolism; D009024:Morphogenesis; D051419:Paxillin / Q000235:genetics / Q000378:metabolism*; D010588:Phagosomes / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D016596:Vinculin / Q000378:metabolism; D014921:Wings, Animal / Q000002:abnormalities / Q000033:anatomy & histology / Q000502:physiology
D029721:Drosophila Proteins; D016023:Integrins; D051419:Paxillin; D011993:Recombinant Fusion Proteins; D016596:Vinculin; C518074:Atg1 protein, Drosophila; D000071189:Autophagy-Related Protein-1 Homolog; D017346:Protein Serine-Threonine Kinases