Within the bodies of mated female mammals and insects, seminal proteins cause biochemical and physiological effects that are important for fertility. Despite their importance, the functions of these proteins are not well understood. We use Drosophila's "Acp" seminal proteins as a model to investigate the mechanisms by which seminal proteins affect females. Acps fall into biochemical classes that are conserved across animals and regulate several analogous reproductive phenomena across animals. Thus, our use of Drosophila genetics to dissect seminal protein function informs the understanding of human fertility and the control of insect vectors of disease. Through genetic tests of over 40 Acps and molecular tests of their function, we have identified individual Acps that regulate specific steps in reproductive processes. We have shown that their action requires molecular or physiological crosstalk between male-derived Acps and molecules or conditions in females. To define precisely how specific Acps work together with the female to mediate their effects, we propose to focus on two steps that occur rapidly after mating in Drosophila. Specifically, we will dissect the role of the Acp ovulin in triggering ovulation by determining its site of action, the role of its processing, the identity of its receptor, and whether ovulin mediates muscle contractions and acts with the biogenic amine octopamine. We will dissect the way in which the seminal protein Acp36DE promotes the entry of sperm into storage by determining its active regions, its receptor, and whether it triggers vesicle release and acts through particular female reproductive tract proteins to cause conformational changes in the female's reproductive tract. Finally, we will define how a proteolytic pathway composed of male- and female-derived components processes ovulin within mated females. Relevance: The seminal proteins of the fruit fly Drosophila are similar in type to those found in people and other animals, and they cause reproductive effects that are analogous across organisms. This allows us to take advantage of the rapid and unusually powerful genetics of Drosophila to quickly and precisely determine how seminal proteins work to facilitate reproduction. Because of the parallels in seminal protein actions across animals, our results will provide information useful to interpret and address the causes of certain human infertilities, and will help to design methods to control the spread of insects that transmit diseases to people.

Public Health Relevance

Seminal proteins are important for fertility in all animals tested, including humans. Having identified the suite of seminal proteins in the powerful model system Drosophila and shown that they regulate specific steps in reproductive pathways, we will dissect how these proteins work together with female cells and proteins in the molecular "dialogues" that we have recently discovered. Because of analogous actions of seminal proteins across animals, our results will inform understanding of certain infertilities in humans, and methods to control the reproduction of insect vectors of human disease.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD038921-13
Application #
8443879
Study Section
Special Emphasis Panel (ZRG1-EMNR-E (02))
Program Officer
Taymans, Susan
Project Start
2000-08-01
Project End
2015-02-28
Budget Start
2013-03-01
Budget End
2014-02-28
Support Year
13
Fiscal Year
2013
Total Cost
$289,711
Indirect Cost
$107,503
Name
Cornell University
Department
Biochemistry
Type
Schools of Arts and Sciences
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Sitnik, Jessica L; Gligorov, Dragan; Maeda, Robert K et al. (2016) The Female Post-Mating Response Requires Genes Expressed in the Secondary Cells of the Male Accessory Gland in Drosophila melanogaster. Genetics 202:1029-41
Schwenke, Robin A; Lazzaro, Brian P; Wolfner, Mariana F (2016) Reproduction-Immunity Trade-Offs in Insects. Annu Rev Entomol 61:239-56
Avila, Frank W; Wong, Alex; Sitnik, Jessica L et al. (2015) Don't pull the plug! the Drosophila mating plug preserves fertility. Fly (Austin) 9:62-7
Gaertner, Bryn E; Ruedi, Elizabeth A; McCoy, Lenovia J et al. (2015) Heritable variation in courtship patterns in Drosophila melanogaster. G3 (Bethesda) 5:531-9
Mattei, Alexandra L; Riccio, Mark L; Avila, Frank W et al. (2015) Integrated 3D view of postmating responses by the Drosophila melanogaster female reproductive tract, obtained by micro-computed tomography scanning. Proc Natl Acad Sci U S A 112:8475-80
Sirot, Laura K; Wong, Alex; Chapman, Tracey et al. (2015) Sexual conflict and seminal fluid proteins: a dynamic landscape of sexual interactions. Cold Spring Harb Perspect Biol 7:a017533
McGraw, Lisa A; Suarez, Susan S; Wolfner, Mariana F (2015) On a matter of seminal importance. Bioessays 37:142-7
Avila, Frank W; Cohen, Allie B; Ameerudeen, Fatima S et al. (2015) Retention of Ejaculate by Drosophila melanogaster Females Requires the Male-Derived Mating Plug Protein PEBme. Genetics 200:1171-9
Avila, Frank W; Mattei, Alexandra L; Wolfner, Mariana F (2015) Sex peptide receptor is required for the release of stored sperm by mated Drosophila melanogaster females. J Insect Physiol 76:1-6
Chow, Clement Y; Avila, Frank W; Clark, Andrew G et al. (2015) Induction of excessive endoplasmic reticulum stress in the Drosophila male accessory gland results in infertility. PLoS One 10:e0119386

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