Abstract
Small Rab GTPases, the largest group of small monomeric GTPases, regulate vesicle trafficking in cells, which are integral to many cellular processes. Their role in neurological diseases, such as cancer and inflammation have been extensively studied, but their implication in kidney disease has not been researched in depth. Rab3a and its effector Rabphillin-3A (Rph3A) expression have been demonstrated to be present in the podocytes of normal kidneys of mice rats and humans, around vesicles contained in the foot processes, and they are overexpressed in diseases with proteinuria. In addition, the Rab3A knockout mice model induced profound cytoskeletal changes in podocytes of high glucose fed animals. Likewise, RphA interference in the Drosophila model produced structural and functional damage in nephrocytes with reduction in filtration capacities and nephrocyte number. Changes in the structure of cardiac fiber in the same RphA-interference model, open the question if Rab3A dysfunction would produce simultaneous damage in the heart and kidney cells, an attractive field that will require attention in the future.
Highlights
Advances in understanding the role of Rab GTPase in the kidney has been obtained from assessing the expression and activity of the exocyst complex in the development and repairing of tubular damage, identified changes in Rab proteins induced by low-frequency genetic nephropathy or hypertension or assessing pathologic expression in models of proteinuria, both glomerular and tubular
Rph3A interference reduces the expression of Rab3a and the Drosophila ortholog of transcription factor Krüppel-like factor 15 (KLF15) is a zincfinger transcription factor highly expressed in the glomeruli and interstitial cells
Our results suggested that the Rab3ARph3A system could be involved in the alterations observed in injured podocytes and that a mechanism may be activated to reduce damage through the vesicular transport enhancement directed by this system
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The role of Rab GTPases in diseases and specific syndromes has been broadly investigated [3]. Each Rab protein has specific effector proteins that regulate distinct intracellular transport steps, which are the trans-Golgi network, endosomal pathway-lysosome for clearance/degradation, or fusion with the cellular membrance for vesicle release being the most studied [4,5,6]. Rabs are associated with inherited genetic and acquired diseases [7]. Their impact on cancer, neurologic disease, immunity, and infections have been recognized [8]. This review provides an overview of the relevance of Rab GTPases in human diseases, with a special focus on the Rab3a-Rph3A complex and its critical role in kidney disease and a mention of future implications
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