Abstract
Phosphoinositides (PIs) play pivotal roles in the regulation of many biological processes. The quality and quantity of PIs is regulated in time and space by the activity of PI kinases and PI phosphatases. The number of PI-metabolizing enzymes exceeds the number of PIs with, in many cases, more than one enzyme controlling the same biochemical step. This would suggest that the PI system has an intrinsic ability to buffer and compensate for the absence of a specific enzymatic activity. However, there are several examples of severe inherited human diseases caused by mutations in one of the PI enzymes, although other enzymes with the same activity are fully functional. The kidney depends strictly on PIs for physiological processes, such as cell polarization, filtration, solute reabsorption, and signal transduction. Indeed, alteration of the PI system in the kidney very often results in pathological conditions, both inherited and acquired. Most of the knowledge of the roles that PIs play in the kidney comes from the study of KO animal models for genes encoding PI enzymes and from the study of human genetic diseases, such as Lowe syndrome/Dent disease 2 and Joubert syndrome, caused by mutations in the genes encoding the PI phosphatases, OCRL and INPP5E, respectively.
Highlights
Phosphoinositides (PIs) play pivotal roles in the regulation of many biological processes
The common view of PI distribution only partially takes into account their transient nature and represents the seven different PIs in the cell according to a “standard” map with PI3,4,5P3 and PI4,5P2 prevalent at the plasma membrane, PI4P at the Golgi complex, and PI3P and PI3,5P2 at endolysosomal compartments [5]
In proximal tubule cell (PTC), fast and efficient recycling of receptors to the apical membrane is necessary for the continuous reabsorption of ligands that would otherwise be lost with the urine
Summary
PIs play a pivotal role in the polarization of epithelial cells. In vitro studies have shown that kidney cells (MDCK) grown in three dimensions are able to polarize and generate a tubule-like structure [10]. The polarization is triggered by the interaction of 1-integrin with collagen in the extracellular matrix This interaction triggers a signaling cascade that involves Rac activation leading to the assembly of laminin at the basement membrane [13]. Basement membrane determination by laminin accumulation generates an intracellular signal that is transmitted to the opposite side of the cell defining it as the apical surface. This signal affects the cytoskeleton with most of the actin accumulating at the apical surface in a region that faces the nascent tubule. The apical PI4,5P2/ Anx2/Cdc complex controls the organization of the subapical actin cytoskeleton, contributing to the establishment of cell polarity [20]. The reduction of PI3,4,5P3 synthesis by PI3-kinase inhibition interferes with the establishment of polarity by reducing the amount of basolateral PI3,4,5P3 levels [21]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
