Published online 2 October 2006. doi:10.1083/jcb.1751iti2
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 175, Number 1, 2-2
Not so close
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When Tuba goes silent (bottom), the plasma membrane droops (arrows).
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Like passengers in a crowded subway car, cells try to limit contact with their neighbors. Otani et al. on page 135 identify a protein that helps cells minimize their closeness by keeping their membranes taut.
Subway passengers can pull in their elbows, but cells in an epithelial layer cannot avoid touching other cells. Instead, they tend to assume a hexagonal shape in which the membrane is stretched tight. Previous studies suggest that the proteins cadherin and actin help structure the adherens junctions that form at the borders where cells meet. The mystery is, what controls the membrane's tension between these intersections?
To find out, Otani et al. investigated the little-studied protein Tuba, which belongs to a group of factors that indirectly regulate actin. The researchers found that Tuba built up at cell edges. Cutting its levels with RNAi caused the cell membrane to sag, indicating that the molecule helps tighten the structure. In normal cells, a mesh of cadherin and actin runs along the inside of the membrane and connects to the adherens junction. But in the Tuba-depleted cells, the cadherin network fractured, and fewer strong, thick actin fibers were present.
Tuba switches on Cdc42, one of the RhoGTPases that regulates actin. Like Tuba, Cdc42 accumulated at cell–cell junctions, the researchers discovered. Reducing Cdc42 activity in cells produced the same cadherin and actin defects as RNAi. But if the Tuba knock-down cells made a hyperactive version of Cdc42, their membranes were taut.
The results suggest that Tuba controls the tension of the cell membrane by adjusting actin polymerization through Cdc42. The finding makes sense, the researchers note, because actin helps regulate the elasticity of the cell surface. The actin network might keep cells in shape by bracing the membrane and helping the boundaries remain straight. 
Mitch Leslie
mitchleslie{at}comcast.net
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Cdc42 GEF Tuba regulates the junctional configuration of simple epithelial cells
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