Calcium Signaling in the Regulation of Flagellar Beating in Sperm

Cornell Univ - State: Awds Made Prior May 2010, Ithaca NY

Investigators

Abstract

Sperm are unique cells with the vital function of propagating the species. Unlike most other cells, they must carry out their function without the ability to activate genes or synthesize proteins. It is amazing to think that mammalian sperm can travel deep into the body of a female and fertilize eggs with only the shirts on their backs, so to speak. How is this accomplished? One behavior that enables sperm to reach the egg and fertilize it is called "hyperactivation". The tails of hyperactivated sperm increase the amplitude of bending on one side. It has been established that this bending pattern provides sperm with additional thrust for penetrating the vestments of the egg; however, it is also thought to assist sperm in reaching the egg. This project has been designed to test whether hyperactivation is required to get sperm to the egg and to determine the mechanism that increases the tail bending. Mutant mice whose sperm lack the ability to hyperactivate will be used to test whether hyperactivation enables sperm to advance towards the egg in the fallopian tube. The behavior of the mutant sperm within mated females will be compared with that of wild-type sperm. This can be accomplished by placing the fallopian tubes on a microscope stage and looking through their transparent walls to chart the progress of the sperm within. Next, in order to examine the mechanism controlling hyperactivation, the role of calcium will be investigated. It has been established that calcium is required by sperm in order to hyperactivate. The objective will be to identify the type of membrane channel that enables calcium to enter sperm and switch on hyperactivation by employing pharmacological agents known to specifically block each type of calcium channel to see which agent prevents calcium influx and subsequent hyperactivation. The final objective of this project will be to identify which components of the tail interact with the protein calmodulin, which is the immediate target of calcium. The merit of this project is that the results obtained should elucidate the function and regulation of hyperactivation, thereby increasing understanding of how mammalian sperm reach the egg to fertilize it. The educational impact will be on individual graduate and undergraduate students, including minority students, who will learn to perform and interpret experiments. In addition, laboratory exercises on the regulation of sperm motility will be presented to high school and undergraduate classes.