Journal article
Pharmaco-Genetic Screen To Uncover Actin Regulators Targeted by Prostaglandins During Drosophila Oogenesis
G3 : genes - genomes - genetics, Vol.9(11), pp.3555-3565
11/01/2019
DOI: 10.1534/g3.119.400704
PMCID: PMC6829128
PMID: 31506320
Abstract
Prostaglandins (PGs) are lipid signaling molecules with numerous physiologic functions, including pain/inflammation, fertility, and cancer. PGs are produced downstream of cyclooxygenase (COX) enzymes, the targets of non-steroidal anti-inflammatory drugs (NSAIDs). In numerous systems, PGs regulate actin cytoskeletal remodeling, however, their mechanisms of action remain largely unknown. To address this deficiency, we undertook a pharmaco-genetic interaction screen during late-stage Drosophila oogenesis. Drosophila oogenesis is as an established model for studying both actin dynamics and PGs. Indeed, during Stage 10B, cage-like arrays of actin bundles surround each nurse cell nucleus, and during Stage 11, the cortical actin contracts, squeezing the cytoplasmic contents into the oocyte. Both of these cytoskeletal properties are required for follicle development and fertility, and are regulated by PGs. Here we describe a pharmaco-genetic interaction screen that takes advantage of the fact that Stage 10B follicles will mature in culture and COX inhibitors, such as aspirin, block this in vitro follicle maturation. In the screen, aspirin was used at a concentration that blocks 50% of the wild-type follicles from maturing in culture. By combining this aspirin treatment with heterozygosity for mutations in actin regulators, we quantitatively identified enhancers and suppressors of COX inhibition. Here we present the screen results and initial follow-up studies on three strong enhancers - Enabled, Capping protein, and non-muscle Myosin II Regulatory Light Chain. Overall, these studies provide new insight into how PGs regulate both actin bundle formation and cellular contraction, properties that are not only essential for development, but are misregulated in disease.
Details
- Title: Subtitle
- Pharmaco-Genetic Screen To Uncover Actin Regulators Targeted by Prostaglandins During Drosophila Oogenesis
- Creators
- Andrew J. Spracklen - Roy J. and Lucille A. Carver College of MedicineMaureen C. Lamb - Roy J. and Lucille A. Carver College of MedicineChristopher M. Groen - Roy J. and Lucille A. Carver College of MedicineTina L. Tootle - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- G3 : genes - genomes - genetics, Vol.9(11), pp.3555-3565
- DOI
- 10.1534/g3.119.400704
- PMID
- 31506320
- PMCID
- PMC6829128
- NLM abbreviation
- G3 (Bethesda)
- ISSN
- 2160-1836
- eISSN
- 2160-1836
- Publisher
- Genetics Society America
- Number of pages
- 11
- Grant note
- MCB-115827 / National Science Foundation; National Science Foundation (NSF) F32GM117803 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) T32CA009156 / NIH Postdoctoral Training Grant in Integrated Training in Cancer Model Systems; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA P30CA086862 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) T32GM067795 / National Institutes of Health (NIH) Predoctoral Training Grant in Pharmacological Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA University of Iowa, Graduate College Summer Fellowship F32GM117803 / NIH Ruth L. Kirschstein National Research Service Award Individual Postdoctoral Fellowship; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA GM116885 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Anatomy and Cell Biology Department Graduate Fellowship
- Language
- English
- Date published
- 11/01/2019
- Academic Unit
- Anatomy and Cell Biology
- Record Identifier
- 9984284451302771
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