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Study offers new clues about hereditary spastic paraplegia
Date:7/8/2011

ow it worked."

Membranes are both the brick walls and the zip-lock bags of microbiology. Every living cell is encased in a water-tight membrane of fatty acids, and all of the cell's interactions with the outside world are mediated by what can and cannot pass through that membrane. When a virus invades a healthy cell, it uses membrane fusion. When a sperm fertilizes an egg, it uses membrane fusion. Membranes are also used inside the cell, where they serve as biochemical reaction chambers, as cargo containers and as pipelines.

To find out how atlastin initiates membrane fusion, McNew, Daga and colleagues conducted experiments involving the fruit-fly version of atlastin, which is remarkably similar to the version found in humans. By selectively disabling portions of the protein and examining how those modifications affected atlastin's ability to promote membrane fusion in the test tube and cell cultures, the team gradually built a picture of how atlastin works. They found that pairs of atlastin proteins, each of which is anchored in a separate membrane, can bind to one another when both partners are functional enzymes. That action draws the separated membranes together and allows fusion to occur.

Additionally, they found that a small piece near the end of atlastin was required for fusion activity.

"Atlastin has a fairly short tail, which protrudes from the site where the protein is anchored into the membrane," Daga said. "When we deleted this tail, we found that the protein could not stimulate membrane fusion, even when the two copies bound together normally."

McNew said prior gene sequencing studies have show that some HSP patients have genetic mutations that result in defects in this critical tail region of the atlastin protein.

"This study, as well as work by others, suggests the area of the cell where atlastin promotes membrane fusion, the endoplasmic reticulum, is a good target for future studies into the caus
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Contact: Jade Boyd
jadeboyd@rice.edu
713-348-6778
Rice University
Source:Eurekalert  

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