MASSACHUSETTS GENERAL HOSPITAL, THE
The present request is for an administrative supplement (RFA: NOT-OO-09-056) to accelerate the pace of the research plan of the parent grant 5ROI 1-10045821-04: "Water and solute transport in the epididymis". The requested funds will be used to hire a post-doctoral fellow, who will perform experiments that will increase scientific progress related to Specific Aim I A: "0 characterize the pathways of apical water and/or neutral solute transport in the epididymis", and Specific Aim 2B: "To examine the regulation of AQP9 permeability" of the parent grant. AQP9 is the main apical aquaporin in the epididymis, and we will characterize its contribution to solute and water transport in epididymal tubules perfused in vivo. We have recently obtained exciting new results that confirm our initial hypothesis that AQP9 is activated by cAMP, an effect that may be mediated via its interaction with CFTR and NIIERF1. We will explore this possibility by using stopped-now light scattering experiments on epididymal apical membrane vesicles and CHO cells expressing human AQP9. The potential roles of PKA, PKC and PKG in AQP9 activation will be examined. We postulate that AQP9 is involved in the establishment of the hypertonic luminal environment that is necessary for the maturation and storage of spermatozoa, as well as in the concentration of spermatozoa that occurs as they transit through this organ. This new fellow will certainly contribute to accelerating the tempo of our research activities. In addition, the creation of this new job opportunity will fulfill the mandate of this RFA to promote economic development.