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Subcellular distribution of Ras GTPase isoforms in normal human kidney.

BACKGROUND
Ras GTPase isoforms have been implicated in proliferative renal disease and are known to have differential cellular expression in kidney. However, their exact subcellular location in various cells is unknown.


METHODS
Immunogold labelling for Ras isoforms (Harvey, Kirsten and Neural) was performed for subcellular localization under electron microscopy in fresh normal kidney specimens, obtained from the opposite pole of kidneys removed for renal cell cancer.


RESULTS
There was prominent staining shown by Ha-Ras only on the glomerular foot processes as compared with basement membrane or the endothelial cells. Mesangial cells showed intense staining in the cytosol with Ha-Ras (absent in the nucleus), minimal staining with Ki-Ras and none with N-Ras. In both the proximal and distal convoluted tubules, there was a clear staining of the mitochondria with Ha-Ras, with mild cytosolic staining with all of the isoforms.


CONCLUSIONS
Ras isoforms have distinct and separate subcellular distributions in normal kidney cells. Understanding the functional aspects of this distribution pattern is essential if Ras is to be targeted by genetic or molecular therapeutic tools.