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Physiol. Rev. 79: 73-98, 1999;
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PHYSIOLOGICAL REVIEWS   Vol. 79 No. 1 January 1999, pp. 73-98
Copyright ©1999 The American Physiological Society

New Perspectives on Mechanisms Involved in Generating Epithelial Cell Polarity

CHARLES YEAMAN, KENT K. GRINDSTAFF, AND W. JAMES NELSON

Department of Molecular and Cellular Physiology, Beckman Center for Molecular and Genetic Medicine, Stanford University School of Medicine, Stanford, California

Yeaman, Charles, Kent K. Grindstaff, and W. James Nelson. New Perspectives on Mechanisms Involved in Generating Epithelial Cell Polarity. Physiol. Rev. 79: 73-98, 1999. --- Polarized epithelial cells form barriers that separate biological compartments and regulate homeostasis by controlling ion and solute transport between those compartments. Receptors, ion transporters and channels, signal transduction proteins, and cytoskeletal proteins are organized into functionally and structurally distinct domains of the cell surface, termed apical and basolateral, that face these different compartments. This review is about mechanisms involved in the establishment and maintenance of cell polarity. Previous reports and reviews have adopted a Golgi-centric view of how epithelial cell polarity is established, in which the sorting of apical and basolateral membrane proteins in the Golgi complex is a specialized process in polarized cells, and the generation of cell surface polarity is a direct consequence of this process. Here, we argue that events at the cell surface are fundamental to the generation of cell polarity. We propose that the establishment of structural asymmetry in the plasma membrane is the first, critical event, and subsequently, this asymmetry is reinforced and maintained by delivery of proteins that were constitutively sorted in the Golgi. We propose a hierarchy of stages for establishing cell polarity.




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 Biol. Reprod.Home page
A. Jablonka-Shariff and I. Boime
Luteinizing Hormone and Follicle-Stimulating Hormone Exhibit Different Secretion Patterns from Cultured Madin-Darby Canine Kidney Cells
Biol Reprod, March 1, 2004; 70(3): 649 - 655.
[Abstract] [Full Text] [PDF]

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 JCBHome page
H. Liu, D. C. Radisky, F. Wang, and M. J. Bissell
Polarity and proliferation are controlled by distinct signaling pathways downstream of PI3-kinase in breast epithelial tumor cells
J. Cell Biol., February 16, 2004; 164(4): 603 - 612.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
J. A. Williams, B. MacIver, E. A. Klipfell, and G. H. Thomas
The C-terminal domain of Drosophila {beta}Heavy-spectrin exhibits autonomous membrane association and modulates membrane area
J. Cell Sci., February 15, 2004; 117(5): 771 - 782.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Lung Cell. Mol. Physiol.Home page
X. Han, M. P. Fink, T. Uchiyama, R. Yang, and R. L. Delude
Increased iNOS activity is essential for pulmonary epithelial tight junction dysfunction in endotoxemic mice
Am J Physiol Lung Cell Mol Physiol, February 1, 2004; 286(2): L259 - L267.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
A. I. Ivanov, A. Nusrat, and C. A. Parkos
Endocytosis of Epithelial Apical Junctional Proteins by a Clathrin-mediated Pathway into a Unique Storage Compartment
Mol. Biol. Cell, January 1, 2004; 15(1): 176 - 188.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
T. Huang, Y. You, M. S. Spoor, E. J. Richer, Vrinda. V. Kudva, R. C. Paige, M. P. Seiler, J. M. Liebler, J. Zabner, C. G. Plopper, et al.
Foxj1 is required for apical localization of ezrin in airway epithelial cells
J. Cell Sci., December 15, 2003; 116(24): 4935 - 4945.
[Abstract] [Full Text] [PDF]

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 Proc. Natl. Acad. Sci. USAHome page
S. C. Brock, J. R. Goldenring, and J. E. Crowe Jr.
Apical recycling systems regulate directional budding of respiratory syncytial virus from polarized epithelial cells
PNAS, December 9, 2003; 100(25): 15143 - 15148.
[Abstract] [Full Text] [PDF]

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 IOVSHome page
S. Narayan, G. Prasanna, R. R. Krishnamoorthy, X. Zhang, and T. Yorio
Endothelin-1 Synthesis and Secretion in Human Retinal Pigment Epithelial Cells (ARPE-19): Differential Regulation by Cholinergics and TNF-{alpha}
Invest. Ophthalmol. Vis. Sci., November 1, 2003; 44(11): 4885 - 4894.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
J. R. Dalby-Payne, E. V. O'Loughlin, and P. Gunning
Polarization of Specific Tropomyosin Isoforms in Gastrointestinal Epithelial Cells and Their Impact on CFTR at the Apical Surface
Mol. Biol. Cell, November 1, 2003; 14(11): 4365 - 4375.
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 JCBHome page
H. Folsch, M. Pypaert, S. Maday, L. Pelletier, and I. Mellman
The AP-1A and AP-1B clathrin adaptor complexes define biochemically and functionally distinct membrane domains
J. Cell Biol., October 27, 2003; 163(2): 351 - 362.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
K. Ebnet, M. Aurrand-Lions, A. Kuhn, F. Kiefer, S. Butz, K. Zander, M.-K. M. z. Brickwedde, A. Suzuki, B. A. Imhof, and D. Vestweber
The junctional adhesion molecule (JAM) family members JAM-2 and JAM-3 associate with the cell polarity protein PAR-3: a possible role for JAMs in endothelial cell polarity
J. Cell Sci., October 1, 2003; 116(19): 3879 - 3891.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
O. Vagin, S. Denevich, and G. Sachs
Plasma membrane delivery of the gastric H,K-ATPase: the role of {beta}-subunit glycosylation
Am J Physiol Cell Physiol, October 1, 2003; 285(4): C968 - C976.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
M. H. Roh and B. Margolis
Composition and function of PDZ protein complexes during cell polarization
Am J Physiol Renal Physiol, September 1, 2003; 285(3): F377 - F387.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
A. K. Rajasekaran and S. A. Rajasekaran
Role of Na-K-ATPase in the assembly of tight junctions
Am J Physiol Renal Physiol, September 1, 2003; 285(3): F388 - F396.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
H. Doerflinger, R. Benton, J. M. Shulman, and D. S. Johnston
The role of PAR-1 in regulating the polarised microtubule cytoskeleton in the Drosophila follicular epithelium
Development, September 1, 2003; 130(17): 3965 - 3975.
[Abstract] [Full Text] [PDF]

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 PhysiologyHome page
W. J. Nelson
Epithelial Cell Polarity From the Outside Looking In
Physiology, August 1, 2003; 18(4): 143 - 146.
[Abstract] [Full Text] [PDF]

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 DevelopmentHome page
C.-c. Huang, D. H. Hall, E. M. Hedgecock, G. Kao, V. Karantza, B. E. Vogel, H. Hutter, A. D. Chisholm, P. D. Yurchenco, and W. G. Wadsworth
Laminin {alpha} subunits and their role in C. elegans development
Development, July 15, 2003; 130(14): 3343 - 3358.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
M. H. Roh, S. Fan, C.-J. Liu, and B. Margolis
The Crumbs3-Pals1 complex participates in the establishment of polarity in mammalian epithelial cells
J. Cell Sci., July 15, 2003; 116(14): 2895 - 2906.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
T. Takeda, H. Yamazaki, and M. G. Farquhar
Identification of an apical sorting determinant in the cytoplasmic tail of megalin
Am J Physiol Cell Physiol, May 1, 2003; 284(5): C1105 - C1113.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Renal Physiol.Home page
L. M. Mangravite, G. Xiao, and K. M. Giacomini
Localization of human equilibrative nucleoside transporters, hENT1 and hENT2, in renal epithelial cells
Am J Physiol Renal Physiol, May 1, 2003; 284(5): F902 - F910.
[Abstract] [Full Text] [PDF]

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 Integr. Comp. Biol.Home page
S. Tyler
Epithelium--The Primary Building Block for Metazoan Complexity
Integr. Comp. Biol., February 1, 2003; 43(1): 55 - 63.
[Abstract] [Full Text] [PDF]

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 Cancer Res.Home page
J. Muschler, D. Levy, R. Boudreau, M. Henry, K. Campbell, and M. J. Bissell
A Role for Dystroglycan in Epithelial Polarization: Loss of Function in Breast Tumor Cells
Cancer Res., December 1, 2002; 62(23): 7102 - 7109.
[Abstract] [Full Text] [PDF]

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 Arch OphthalmolHome page
C. J. Lee, P. Huie, T. Leng, M. C. Peterman, M. F. Marmor, M. S. Blumenkranz, S. F. Bent, and H. A. Fishman
Microcontact Printing on Human Tissue for Retinal Cell Transplantation
Arch Ophthalmol, December 1, 2002; 120(12): 1714 - 1718.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
D. Karnak, S. Lee, and B. Margolis
Identification of Multiple Binding Partners for the Amino-terminal Domain of Synapse-associated Protein 97
J. Biol. Chem., November 22, 2002; 277(48): 46730 - 46735.
[Abstract] [Full Text] [PDF]

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 Mol Hum ReprodHome page
C. Heneweer, L. H. Kruse, F. Kindhauser, M. Schmidt, K. H. Jakobs, H.-W. Denker, and M. Thie
Adhesiveness of human uterine epithelial RL95-2 cells to trophoblast: Rho protein regulation
Mol. Hum. Reprod., November 1, 2002; 8(11): 1014 - 1022.
[Abstract] [Full Text] [PDF]

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 J. Biol. Chem.Home page
C. He, M. Hobert, L. Friend, and C. Carlin
The Epidermal Growth Factor Receptor Juxtamembrane Domain Has Multiple Basolateral Plasma Membrane Localization Determinants, Including a Dominant Signal with a Polyproline Core
J. Biol. Chem., October 4, 2002; 277(41): 38284 - 38293.
[Abstract] [Full Text] [PDF]

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 Mol. Biol. CellHome page
P. L. Tuma, L. K. Nyasae, and A. L. Hubbard
Nonpolarized Cells Selectively Sort Apical Proteins from Cell Surface to a Novel Compartment, but Lack Apical Retention Mechanisms
Mol. Biol. Cell, October 1, 2002; 13(10): 3400 - 3415.
[Abstract] [Full Text] [PDF]

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 J. Cell Sci.Home page
A. Suzuki, C. Ishiyama, K. Hashiba, M. Shimizu, K. Ebnet, and S. Ohno
aPKC kinase activity is required for the asymmetric differentiation of the premature junctional complex during epithelial cell polarization
J. Cell Sci., September 15, 2002; 115(18): 3565 - 3573.
[Abstract] [Full Text] [PDF]

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 JCBHome page
E. Medina, J. Williams, E. Klipfell, D. Zarnescu, G. Thomas, and A. Le Bivic
Crumbs interacts with moesin and {beta}Heavy-spectrin in the apical membrane skeleton of Drosophila
J. Cell Biol., September 3, 2002; 158(5): 941 - 951.
[Abstract] [Full Text] [PDF]

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 Infect. Immun.Home page
C. H. Davis, J. E. Raulston, and P. B. Wyrick
Protein Disulfide Isomerase, a Component of the Estrogen Receptor Complex, Is Associated with Chlamydia trachomatis Serovar E Attached to Human Endometrial Epithelial Cells
Infect. Immun., July 1, 2002; 70(7): 3413 - 3418.
[Abstract] [Full Text] [PDF]

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 Am. J. Physiol. Cell Physiol.Home page
S. Gopalakrishnan, K. W. Dunn, and J. A. Marrs
Rac1, but not RhoA, signaling protects epithelial adherens junction assembly during ATP depletion
Am J Physiol Cell Physiol, July 1, 2002; 283(1): C261 - C272.
[Abstract] [Full Text] [PDF]


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