PgmNr D1119: A genetic screen for novel neuronal genes regulating lifespan extension in Drosophila melanogaster.

Authors:
T. Chen; W. Lien; C. Chan


Institutes
National Taiwan University, Taipei, Taiwan.


Keyword: metabolism

Abstract:

Rab27 is a neuron-specific GTPase expressing in a small subset of brain neurons in Drosophila melanogaster. Recently we found that loss of rab27 leads to lifespan extension and this effect is dosage-dependent. To discover the genetic network regulating lifespan extension within rab27-expressing neurons, we perform an F1 modifier screen. The rab27Gal4-KO allele is not only a null, but also possesses Gal4 activity that allows for expression within rab27- expressing neurons including the Mushroom bodies and the Insulin-producing cells. In heterozygous rab27KO background, approximately 2000 GS lines would be expressed by rab27Gal4-KO to identify modifiers of rab27-independent longevity phenotype. Similarly, a screen in hemizygous rab27Gal4-KO background was performed to identify novel rab27-independent regulators of lifespan. Known lifespan regulators such as hsp27 and S6K were isolated from the screen, indicating the validity of the screen. For secondary screen, we set a statistical cutoff to determine top candidates. To distinguish the neuron-specific lifespan extensors, genes that extend lifespan via expression from fat bodies were excluded. To examine whether these genes exerts neuronal or organismic protection, both paraquat- and starvation-induced oxidative stress tests were performed. To reveal the underlying mechanisms, further examinations are ongoing, including metabolic analyses of hemolymph glucose and stored energy of TAG. In vivo analyses of several neuron-specific stress-resistant genes will be presented.