The vectorial active transport of solutes and water across epithelial membranes results from the different morphological, biochemical and functional properties of the apical and basolateral aspects of the plasma cell membrane. Though cell polarization is implicit as the main premise in practically all the current models which have been proposed to explain the transepithelial active transport, the mechanisms involved in its subcellular and molecular development have not been elucidated.
The aim of this research proposal is to understand the processes involved in the genesis and development of the epithelial cell polarization. The approach includes the use of cultured epithelial cell lines of renal origin that, like their """"""""in vivo"""""""" counterpart, are able to perform transepthelial active transport. The development of epithelial cell polarization will be studied by monitoring different polarization markers during the conversion of a population of isolated cells into an epithelial membrane. In particular we intend to characterize the factors involved in the determination (signalling) of the polarization process by culturing the cells in interphases of different composition. We will determine which of the pathways proposed to explain the intracellular transport of membranes or macromolecules is or are involved in the assymetrical distribution of the membrane components. A combination of immunochemical, histochemical, and cell fractionation techniques will be used to approach this issue. Finally, we will analyze the mechanisms involved in the integration of polarization markers into the cell membrane. Different transport systems that become evident after their insertion in the cell membrane will be used in the analysis of this step.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK027401-08
Application #
3228288
Study Section
Physiology Study Section (PHY)
Project Start
1980-12-01
Project End
1990-06-30
Budget Start
1988-07-01
Budget End
1990-06-30
Support Year
8
Fiscal Year
1988
Total Cost
Indirect Cost
Name
Massachusetts General Hospital
Department
Type
DUNS #
City
Boston
State
MA
Country
United States
Zip Code
02199
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Viniegra, S; Cragoe Jr, E J; Rabito, C A (1992) Heterogeneity of the Na(+)-H+ antiport systems in renal cells. Biochim Biophys Acta 1106:99-109
Viniegra, S; Rabito, C A (1988) Development and polarization of the Na+/H+ antiport system during reorganization of LLC-PK1A cells into an epithelial membrane. J Biol Chem 263:7099-104
Schneeberger, E E; Lynch, R D; Kelly, C A et al. (1988) Modulation of tight junction formation in clone 4 MDCK cells by fatty acid supplementation. Am J Physiol 254:C432-40