'Dual Control' Strategy Assures Accurate Cellular Marching Orders, But A Pathogenic Microbe Can Hijack The System

In an effort to discover how cells "decide" when and where to move, scientists have uncovered a molceular strategy evolved in mammals to assure control of cellular marching orders. But the strategy appears to be exploited by a microbe that hijacks a cell's molecular motors to attack its human host.

The research by biochemists at the University of California San Francisco is reported in the May 14 issue of the journal Cell.

Regulated movement at the cellular level is critical for survival.

Cells divide, migrate toward food and away from danger. Nerve axons grow and immune armies attack -- all in response to orders from a family of molecules known as organizing or signaling proteins. These proteins are thought to translate selected signals into commands that engage the cell's gears of motion. The pathogenic, food-borne bacterium Listeria monocytogenes, which can cause meningitis and other serious illnesses, is known to recruit the motility apparatus of its human host cells. It uses this engine to power a rocket-like tail and propel itself along a route of infection from one cell to the next.

By studying the three-dimensional structure of a mouse organizing protein called "Enabled" and analyzing its chemical interactions with one of Listeria's proteins, the UCSF scientists found that the microbe's success may lie in its ability to mimic a dual molecular docking maneuver that takes place in mammalian cells, most likely evolved to reduce the chance the cells will march to the wrong orders.

Under normal conditions, the Enabled protein links to receptors near the cell membrane when it receives an external signal to move. Then the organizing protein recruits and mobilizes the cell's motility protein, actin. The cell will then move in the direction that corresponds to the buildup of actin.

The researchers found that in addition to its chemical and structural attraction to the receptor, Enabled also appears to be simultaneously attracted to cell m

Contact: Wallace Ravven
University of California - San Francisco

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