Abstract

Despite considerable effort and characterization, the precise role of PKA in regulating sperm development arid the acquisition of motility and fertilization competence remains unclear. A major roadblock in these studies has been the lack of techniques to manipulate the expression and activity of PKA in sperm cells since no readily accessible cell culture model is available that allows genetic intervention. This proposal continues our efforts to apply mouse genetic approaches to modify the subunits of PKA and address questions that relate to the importance of subcellular localization, PKA activation state, and developmental changes in subunit isoforms.
The specific aims of our proposal include: (1) Analyze the role of S-AKAP84/D-AKAP1 in the development and survival of spermatids (2) Determine the role of C subunit during spermatogenesis (3) Examine the anchoring of Rl and its physiological significance during spermatogenesis (4) Identify specific PKA substrates in sperm and develop a mechanism to inhibit sperm PKA In vivo. These studies are relevant to larger questions concerning the treatment of infertility and the development of male-specific contraceptive approaches.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54HD012629-31
Application #
8062095
Study Section
Project Start
Project End
Budget Start
2010-04-01
Budget End
2011-03-31
Support Year
31
Fiscal Year
2010
Total Cost
$270,020
Indirect Cost

  Institution

Name
University of Washington
Department
Type
DUNS #
605799469
City
Seattle
State
WA
Country
United States
Zip Code
98195

  Publications

Chakraborty, Papia; Buaas, F William; Sharma, Manju et al. (2014) LIN28A marks the spermatogonial progenitor population and regulates its cyclic expansion. Stem Cells 32:860-73
Sanz, Elisenda; Evanoff, Ryan; Quintana, Albert et al. (2013) RiboTag analysis of actively translated mRNAs in Sertoli and Leydig cells in vivo. PLoS One 8:e66179
Cazorla, Maxime; Shegda, Mariya; Ramesh, Bhavani et al. (2012) Striatal D2 receptors regulate dendritic morphology of medium spiny neurons via Kir2 channels. J Neurosci 32:2398-409
Gill, John C; Navarro, Víctor M; Kwong, Cecilia et al. (2012) Increased neurokinin B (Tac2) expression in the mouse arcuate nucleus is an early marker of pubertal onset with differential sensitivity to sex steroid-negative feedback than Kiss1. Endocrinology 153:4883-93
Anawalt, Bradley D; Hotaling, James M; Walsh, Thomas J et al. (2012) Performance of total testosterone measurement to predict free testosterone for the biochemical evaluation of male hypogonadism. J Urol 187:1369-73
Navarro, Victor M; Ruiz-Pino, Francisco; Sanchez-Garrido, Miguel A et al. (2012) Role of neurokinin B in the control of female puberty and its modulation by metabolic status. J Neurosci 32:2388-97
Navarro, V M; Gottsch, M L; Wu, M et al. (2011) Regulation of NKB pathways and their roles in the control of Kiss1 neurons in the arcuate nucleus of the male mouse. Endocrinology 152:4265-75
Navarro, Victor M; Castellano, Juan M; McConkey, Sarah M et al. (2011) Interactions between kisspeptin and neurokinin B in the control of GnRH secretion in the female rat. Am J Physiol Endocrinol Metab 300:E202-10
Gottsch, Michelle L; Popa, Simina M; Lawhorn, Janessa K et al. (2011) Molecular properties of Kiss1 neurons in the arcuate nucleus of the mouse. Endocrinology 152:4298-309
Kim, Joshua; Semaan, Sheila J; Clifton, Donald K et al. (2011) Regulation of Kiss1 expression by sex steroids in the amygdala of the rat and mouse. Endocrinology 152:2020-30

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