RESUMEN
Lipid metabolism plays a critical role in female reproduction. During oogenesis, maturing oocytes accumulate high levels of neutral lipids that are essential for both energy production and the synthesis of other lipid molecules. Metabolic pathways within the ovary are partially regulated by protein kinases that link metabolic status to oocyte development. Although the functions of several kinases in this process are well established, the roles that many other kinases play in coordinating metabolic state with female germ cell development are unknown. Here, we demonstrate that the catalytic activity of casein kinase 2 (CK2) is essential for Drosophila oogenesis. Using an unbiased biochemical screen that leveraged an unusual catalytic property of the kinase, we identified a novel CK2 substrate in the Drosophila ovary, the lipid droplet-associated protein Jabba. We show that Jabba is essential for modulating ovarian lipid metabolism and for regulating female fertility in the fly. Our findings shed light on a CK2-dependent signaling pathway governing lipid metabolism in the ovary and provide insight into the long-recognized but poorly understood association between energy metabolism and female reproduction.
Asunto(s)
Proteínas Portadoras/metabolismo , Quinasa de la Caseína II/metabolismo , Proteínas de Drosophila/metabolismo , Regulación del Desarrollo de la Expresión Génica , Metabolismo de los Lípidos , Oogénesis , Ovario/metabolismo , Células 3T3-L1 , Animales , Animales Modificados Genéticamente , Proteínas Portadoras/química , Proteínas Portadoras/genética , Quinasa de la Caseína II/antagonistas & inhibidores , Quinasa de la Caseína II/química , Quinasa de la Caseína II/genética , Cruzamientos Genéticos , Proteínas de Drosophila/antagonistas & inhibidores , Proteínas de Drosophila/química , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Femenino , Proteínas Fluorescentes Verdes/química , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Células HEK293 , Humanos , Ratones , Microscopía Fluorescente , Ovario/citología , Ovario/enzimología , Fragmentos de Péptidos/química , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/metabolismo , Interferencia de ARN , Proteínas Recombinantes de Fusión/metabolismo , Especificidad por SustratoRESUMEN
Stem cells cycle between periods of quiescence and proliferation to promote tissue health. In Drosophila ovaries, quiescence to proliferation transitions of follicle stem cells (FSCs) are exquisitely feeding-dependent. Here, we demonstrate feeding-dependent induction of follicle cell differentiation markers, eyes absent (Eya) and castor (Cas) in FSCs, a patterning process that does not depend on proliferation induction. Instead, FSCs extend micron-scale cytoplasmic projections that dictate Eya-Cas patterning. We identify still life and sickie as necessary and sufficient for FSC projection growth and Eya-Cas induction. Our results suggest that sequential, interdependent events establish long-term differentiation patterns in follicle cell precursors, independently of FSC proliferation induction.
Asunto(s)
Proteínas de Drosophila , Ovario , Animales , Femenino , Ovario/metabolismo , Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Proteínas de Drosophila/genética , Proteínas de Drosophila/metabolismo , División Celular , Diferenciación CelularRESUMEN
Citizen science is a productive approach to include non-scientists in research efforts that impact particular issues or communities. In most cases, scientists at advanced career stages design high-quality, exciting projects that enable citizen contribution, a crowdsourcing process that drives discovery forward and engages communities. The challenges of having citizens design their own research with no or limited training and providing access to laboratory tools, reagents, and supplies have limited citizen science efforts. This leaves the incredible life experiences and immersion of citizens in communities that experience health disparities out of the research equation, thus hampering efforts to address community health needs with a full picture of the challenges that must be addressed. Here, we present a robust and reproducible approach that engages participants from Grade 5 through adult in research focused on defining how diet impacts disease signaling. We leverage the powerful genetics, cell biology, and biochemistry of Drosophila oogenesis to define how nutrients impact phenotypes associated with genetic mutants that are implicated in cancer and diabetes. Participants lead the project design and execution, flipping the top-down hierarchy of the prevailing scientific culture to co-create research projects and infuse the research with cultural and community relevance.