? ? Renal cell function requires the maintenance of polarized plasma membrane domains with distinct protein and lipid compositions. This is accomplished in part by the targeted delivery of newly synthesized and recycling membrane proteins to the apical or basolateral surface. Apical sorting signals are extraordinarily diverse and include peptide-, lipid- and glycan-dependent motifs. Interestingly, recent data from our and other laboratories suggest that apical proteins with different targeting signals traffic to the surface in distinct populations of transport carriers. These post-Golgi carriers may traffic directly to the cell surface; however, recent studies suggest that some newly-synthesized proteins transit recycling endosomes en route to the cell surface. Our long term goals are to identify the signals that direct apical delivery of newly- synthesized proteins, and to understand how these signals are interpreted at various stages along the biosynthetic and postendocytic pathways.
The aims of this proposal are to identify proteins that regulate distinct pathways to the apical surface in renal epithelial cells, to assess the role of endocytic compartments in the polarized biosynthetic traffic of different classes of apical proteins, and to dissect the mechanism of glycan-dependent sorting along the biosynthetic and postendocytic pathways. The results of our studies will refine our understanding of how transport cues on physiologically relevant molecules are interpreted at distinct intracellular sites to enable proper sorting. ? ? PROJECT NARRATIVE ? The primary function of the kidney is the reabsorption of water, ions, and metabolites from the forming urine to the bloodstream. The surfaces of kidney cells are subdivided into different domains that face the urine and bloodstream and which contain distinct proteins and lipids; and this asymmetric distribution of surface components is essential for proper kidney function. Our goal is to understand how kidney cells create and maintain these distinct surface domains. The results of our research will provide critical basic information that can be applied to the design of potential therapies to combat kidney-related diseases including renal carcinoma, acute renal failure, and hypertension. ? ? ?

National Institute of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Research Project (R01)
Project #
Application #
Study Section
Cellular and Molecular Biology of the Kidney Study Section (CMBK)
Program Officer
Mullins, Christopher V
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of Pittsburgh
Internal Medicine/Medicine
Schools of Medicine
United States
Zip Code
Mattila, Polly E; Raghavan, Venkatesan; Rbaibi, Youssef et al. (2014) Rab11a-positive compartments in proximal tubule cells sort fluid-phase and membrane cargo. Am J Physiol Cell Physiol 306:C441-9
Labilloy, Anatália; Youker, Robert T; Bruns, Jennifer R et al. (2014) Altered dynamics of a lipid raft associated protein in a kidney model of Fabry disease. Mol Genet Metab 111:184-92
Raghavan, Venkatesan; Rbaibi, Youssef; Pastor-Soler, Núria M et al. (2014) Shear stress-dependent regulation of apical endocytosis in renal proximal tubule cells mediated by primary cilia. Proc Natl Acad Sci U S A 111:8506-11
Szalinski, Christina M; Labilloy, Anatália; Bruns, Jennifer R et al. (2014) VAMP7 modulates ciliary biogenesis in kidney cells. PLoS One 9:e86425
Razawi, Hanieh; Kinlough, Carol L; Staubach, Simon et al. (2013) Evidence for core 2 to core 1 O-glycan remodeling during the recycling of MUC1. Glycobiology 23:935-45
Youker, Robert T; Bruns, Jennifer R; Costa, Simone A et al. (2013) Multiple motifs regulate apical sorting of p75 via a mechanism that involves dimerization and higher-order oligomerization. Mol Biol Cell 24:1996-2007
Mo, Di; Ihrke, Gudrun; Costa, Simone A et al. (2012) Apical targeting and endocytosis of the sialomucin endolyn are essential for establishment of zebrafish pronephric kidney function. J Cell Sci 125:5546-54
Mattila, Polly E; Youker, Robert T; Mo, Di et al. (2012) Multiple biosynthetic trafficking routes for apically secreted proteins in MDCK cells. Traffic 13:433-42
Mo, Di; Costa, Simone A; Ihrke, Gudrun et al. (2012) Sialylation of N-linked glycans mediates apical delivery of endolyn in MDCK cells via a galectin-9-dependent mechanism. Mol Biol Cell 23:3636-46
Rondanino, Christine; Poland, Paul A; Kinlough, Carol L et al. (2011) Galectin-7 modulates the length of the primary cilia and wound repair in polarized kidney epithelial cells. Am J Physiol Renal Physiol 301:F622-33

Showing the most recent 10 out of 24 publications