Epithelial cells form membrane sheets which serve as a interface between tissue compartments. The transport of specific macromolecules across this barrier is critical to the proper functioning of most tissues. In order to accomplish specific and directional transport, the plasma membrane of epithelial cells is divided into two subdomains; apical facing the exterior environment or the tissue lumen, and basolateral facing other epithelial cells and the extracellular matrix. These domains maintain distinct protein compositions, and trafficking at each of these domains is uniquely regulated. Regulation of vesicle transport is carried out by small GTPases of the Ras superfamily, including ADP-ribosylation factors (ARFs). One ARF protein, ARF6, functions in the endocytic pathway in non-polarized cells and seems likely to regulate endocytosis at the apical pole of polarized epithelial cells. The overall aim of this proposal is to define the role of ARF6 and a potential downstream effector, phospholipase D, in endocytosis at the apical pole of polarized epithelial cells.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
7F32DK009924-02
Application #
6146803
Study Section
Biological Sciences 2 (BIOL)
Program Officer
Podskalny, Judith M,
Project Start
1999-04-01
Project End
Budget Start
1999-09-01
Budget End
2000-03-31
Support Year
2
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Virginia
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Santy, Lorraine C (2002) Characterization of a fast cycling ADP-ribosylation factor 6 mutant. J Biol Chem 277:40185-8
Santy, L C; Casanova, J E (2001) Activation of ARF6 by ARNO stimulates epithelial cell migration through downstream activation of both Rac1 and phospholipase D. J Cell Biol 154:599-610
Santy, L C; Frank, S R; Hatfield, J C et al. (1999) Regulation of ARNO nucleotide exchange by a PH domain electrostatic switch. Curr Biol 9:1173-6