Molecular Mechanism Found for Size Regulation

A family of enzymes called Rho GTPases regulates several aspects of tissue morphogenesis during animal development. In a study published in the May 2002 issue of Developmental Cell, researchers describe their role in the control of animal size.

The investigation, designed to examine the function of the p190-B Rho-GAP protein, was conducted at Harvard Medical School (Boston MA, USA). This molecule is a known activator of the family of Rho proteins that have been implicated in many cellular processes, including motility, gene expression, proliferation, and cellular shape change.

Genetically engineered mice lacking the p190-B Rho-GAP protein were found to be 30% reduced in size, and exhibited developmental defects strikingly similar to those seen in mice lacking the CREB (cAMP response element binding protein) transcription factor. In p190-B RhoGAP-deficient mice, CREB phosphorylation is substantially reduced in embryonic tissues. Embryo-derived cells contain abnormally high levels of active Rho protein, are reduced in size, and exhibit defects in CREB activation upon exposure to insulin or IGF-1.

These results indicate that Rho and CREB are novel regulators of cell and animal size in the developing mouse, and the authors conclude that Rho modulates a chemical growth signal from the cell membrane to CREB. Although the researchers caution that the signaling pathway is extremely complex, they propose that their results are a significant step forward in understanding the molecular basis of size regulation.



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