"Caspases are needed for the elimination of the majority of the cytoplasm and organelles to make mature sperm," says Steller. "Rather than having death of the whole cell, there is death of only part of the cell. This is clear evidence that this process is conserved from fruit flies to mammals."
The Septin 4 gene, which is missing in the mice with defective sperm, makes both the Septin 4 protein and a protein called ARTS. This second protein is important for activating the death enzymes. The Septin 4 protein, part of a family of proteins first discovered in yeast, is important for making large cytoplasmic scaffolds, similar to construction scaffolding, in cells where proteins can assemble. The scaffolds provide a framework in the cell that helps to compartmentalize different proteins in the cell.
"The Septin 4 protein is normally found in a structure called the annulus in the sperm," says Steller. "The annulus was predicted to be a way to make different compartments in the sperm, and the mutant mice completely lack an annulus. If you normally have to keep all of the proteins in the right compartment, messing that up leads to a number of problems with the sperm, including bent tails and an inability to swim."
Co-author Gary Hunnicutt, Ph.D., the senior collaborative scientist at the Population Council, studies surface compartmentalization and function of sperm.
"Sperm, unlike other cells in the body, must respond and react to a host of different environments in both the male and female reproductive tracts," says Hunnicutt. "Yet they do this without making any new proteins. Instead, they appear to change their functions by rearranging the molecules on their surfaces. The annulus has been thought to act as a gatekeeper that separate
'"/>
Contact: Kristine A. Kelly
kkelly@rockefeller.edu
212-327-7146
Rockefeller University
21-Mar-2005