A Rhesus Factor Protein Channels Extra Acids

Author:  Dunia Rassy
Institution:  London School of Hygiene and Tropical Medicine
Date:  December 2008

If you know what blood group you belong to, you might have noticed a plus or a minus sign next to your group; A, B, AB, or O. This plus or minus sign refers to the presence or absence, accordingly, of a protein in the surface of your red blood cells called a Rhesus factor (abbreviated as Rh). A different Rh group between a mother and the baby she is expecting may lead to the production of antibodies by the mother, while the unborn baby may suffer organ enlargement and anemia. However, besides being used as a compatibility marker in blood, scientists had no clue if the actual Rhesus proteins were involved somehow in body function until last month. Anna Maria Marini and her team published in the November 20 issue of Nature evidence showing that a protein belonging to the Rhesus factor family called RHCG controls acidity levels in the kidney and in the male genital tract.

In order to produce proteins, organisms need nitrogen sources from the environment such as ammonia (NH3) or its protonated-with an extra hydrogen-form, ammonia (NH4). While microbes and plants use up both compounds, animals need to get rid of their surplus, and it is thus transported to the kidneys to be excreted as urine. Excess ammonia in the body acidifies blood and may cause confusion and coma. Some years ago Marini found a gene responsible for ammonia transport in yeast, so when they stumbled upon an almost identical gene in mammals which happened to be Rhesus factor RHCG, she was able to predict its function. Her team was just a few experiments away of finding out if RHCG controlled ammonia flows in the body.

The researchers produced mice lacking the gene for RHCG, which is normally found in the kidneys, the liver, and the genital tract. They found out that RHCG-deficient mice produced urine containing just about a fifth of the normal ammonia excreted; their blood became acid, and they experienced weight loss. The effects, especially blood acidity, were exacerbated if acids were included in the mice's diet, and matched perfectly to symptoms from a human renal disease known as "distal renal tubular acidosis". Following these results Marini thinks the genetically modified mice could be used as a lab model to find cures for the disease.

Moreover, suppressing the functions of RHCG decreased the reproductive functions of the male mice. Their litters were smaller, more fluid and acidic from the genital tract. Without RHCG, there was an excessive ammonia secretion in the testes leading to the release of immature sperm cells. The team therefore believes that the task of RHCG in the testes is to trap the extra ammonia, while still providing a mildly acid environment which allows sperm cells to mature properly.

Results at both sites suggest that RHCG is a channel through which most of the ammonia circulates in our bodies, not a passive role after all. Marini would still like to study RHCG's function in other tissues, but physiology textbooks will already need to reform the old vision which proposed that ammonia traveled freely between cells.

Written by: Dunia Rassy

Edited by: Jeffrey Kost

Published by: Hoi See Tsao