Polarized exocytosis is an essential process in many organisms and cell types for correct cell division or functional specialization. Previous studies established that homologs of the oxysterol-binding protein (OSBP) in , which comprise the Osh protein family, are necessary for efficient polarized exocytosis by supporting a late post-Golgi step. We define this step as the docking of a specific sub-population of exocytic vesicles with the plasma membrane. In the absence of other Osh proteins, yeast Osh4p can support this process in a manner dependent upon two lipid ligands, PI4P and sterol. Osh6p, which binds PI4P and phosphatidylserine, is also sufficient to support polarized exocytosis, again in a lipid-dependent manner. These data suggest that Osh-mediated exocytosis depends upon lipid binding and exchange without a strict requirement for sterol. We propose a two-step mechanism for Osh protein-mediated regulation of polarized exocytosis by using Osh4p as a model. We describe a specific role for lipid binding by an OSBP-related protein (ORP) in the process of polarized exocytosis, guiding our understanding of where and how OSBP and ORPs may function in more complex organisms.
Background: Acute kidney injury affects nearly 30% of preterm neonates in the intensive care unit. We aimed to determine if nephrotoxin-induced AKI disrupted renal development assessed by imaging (CFE-MRI). Methods: Neonatal New Zealand rabbits received indomethacin and gentamicin (AKI) or saline (control) for four days followed by cationic ferritin (CF) at six weeks. Ex vivo images were acquired using a gradient echo pulse sequence on 7T MRI. Glomerular number (N glom) and apparent glomerular volume (aV glom) were determined. CF toxicity was assessed at 2 and 28 days in healthy rabbits. Results: N glom was lower in the AKI group as compared to controls (74,034 vs 198,722, p<0.01). aV glom was not different (AKI:7.3 ×10 −4 vs. control: 6.2 ×10 −4 mm 3 , p=0.69). AKI kidneys had a band of glomeruli distributed radially in the cortex that were undetectable by MRI. Following CF injection, there was no difference in body or organ weights except for the liver, and transient changes in serum iron, platelets and white blood cell count. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:
AKI is common and associated with poor outcomes. It is probable that AKI is a harbinger to CKD in pediatric populations. However, we currently lack the tools to definitely answer this question and more research is needed.
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