Protein trafficking and polarity in kidney epithelium: from cell biology to physiology

1996 ◽  
Vol 76 (1) ◽  
pp. 245-297 ◽  
Author(s):  
D. Brown ◽  
J. L. Stow

The transepithelial movement of fluids, electrolytes, and larger molecules is achieved by the activity of a host of specialized transporting proteins, including enzymes, receptors, and channels, that are located on either the apical, basal, or lateral plasma membrane domains of epithelial cells. In the kidney as well as in all other organs, this remarkable polarity of epithelial cells depends on the selective insertion of newly synthesized and recycling proteins and lipids into distinct plasma membrane domains and on the maintenance and modulation of these specialized domains once they are established during epithelial development. This review addresses the mechanisms by which epithelial cells control the movement of membrane components within the cell to ensure that they are delivered to the correct target membrane. Among the topics discussed are targeting signals within membrane proteins, the role of the cytoskeleton and the tight junctional barrier in cell polarity, and the requirement for accessory proteins in the targeting process, including GTP-binding proteins, and proteins that are involved in vesicle docking and fusion events. The final part of the review is devoted uniquely to the polarized targeting of functionally defined proteins in various kidney cell types. In concluding, examples of how a breakdown in these trafficking pathways may be related to some disease states are presented.

Author(s):  
J.M. Robinson ◽  
J.M Oliver

Specialized regions of plasma membranes displaying lateral heterogeneity are the focus of this Symposium. Specialized membrane domains are known for certain cell types such as differentiated epithelial cells where lateral heterogeneity in lipids and proteins exists between the apical and basolateral portions of the plasma membrane. Lateral heterogeneity and the presence of microdomains in membranes that are uniform in appearance have been more difficult to establish. Nonetheless a number of studies have provided evidence for membrane microdomains and indicated a functional importance for these structures.This symposium will focus on the use of various imaging modalities and related approaches to define membrane microdomains in a number of cell types. The importance of existing as well as emerging imaging technologies for use in the elucidation of membrane microdomains will be highlighted. The organization of membrane microdomains in terms of dimensions and spatial distribution is of considerable interest and will be addressed in this Symposium.


2004 ◽  
Vol 72 (9) ◽  
pp. 5349-5357 ◽  
Author(s):  
Richard C. Laughlin ◽  
Glen C. McGugan ◽  
Rhonda R. Powell ◽  
Brenda H. Welter ◽  
Lesly A. Temesvari

ABSTRACT Lipid rafts are highly ordered, cholesterol-rich, and detergent-resistant microdomains found in the plasma membrane of many eukaryotic cells. These domains play important roles in endocytosis, secretion, and adhesion in a variety of cell types. The parasitic protozoan Entamoeba histolytica, the causative agent of amoebic dysentery, was determined to have raft-like plasma membrane domains by use of fluorescent lipid analogs that specifically partition into raft and nonraft regions of the membrane. Disruption of raft-like membrane domains in Entamoeba with the cholesterol-binding agents filipin and methyl-β-cyclodextrin resulted in the inhibition of several important virulence functions, fluid-phase pinocytosis, and adhesion to host cell monolayers. However, disruption of raft-like domains did not inhibit constitutive secretion of cysteine proteases, another important virulence function of Entamoeba. Flotation of the cold Triton X-100-insoluble portion of membranes on sucrose gradients revealed that the heavy, intermediate, and light subunits of the galactose-N-acetylgalactosamine-inhibitible lectin, an important cell surface adhesion molecule of Entamoeba, were enriched in cholesterol-rich (raft-like) fractions, whereas EhCP5, another cell surface molecule, was not enriched in these fractions. The subunits of the lectin were also observed in high-density, actin-rich fractions of the sucrose gradient. Together, these data suggest that pinocytosis and adhesion are raft-dependent functions in this pathogen. This is the first report describing the existence and physiological relevance of raft-like membrane domains in E. histolytica.


2000 ◽  
Vol 278 (2) ◽  
pp. F192-F201 ◽  
Author(s):  
Dennis Brown

Epithelial cells in the kidney have highly specialized transport mechanisms that differ among the many tubule segments, and among the different cell types that are present in some regions. The purpose of this brief review is to examine some of the major intracellular mechanisms by which the membrane proteins that participate in these differentiated cellular functions are addressed, sorted, and delivered to specific membrane domains of epithelial cells. Unraveling these processes is important not only for our understanding of normal cellular function but is also critical for the interpretation of pathophysiological dysfunction in the context of newly generated molecular and cellular information concerning hereditary and acquired transporter abnormalities. Among the topics covered are sorting signals on proteins, role of the cytoskeleton, vesicle coat proteins, the fusion machinery, and exo- and endocytosis of recycling proteins. Examples of these events in renal epithelial cells are highlighted throughout this review and are related to the physiology of the kidney.


Biochemistry ◽  
1999 ◽  
Vol 38 (1) ◽  
pp. 142-150 ◽  
Author(s):  
Thomas Pomorski ◽  
Andreas Herrmann ◽  
Peter Müller ◽  
Gerrit van Meer ◽  
Koert Burger

1998 ◽  
Vol 46 (2) ◽  
pp. 241-248 ◽  
Author(s):  
Anna-Liisa Tuhkanen ◽  
Markku Tammi ◽  
Alpo Pelttari ◽  
Ulla M. Ågren ◽  
Raija Tammi

We used immunogold staining and stereology to examine the ultrastructural localization and to estimate the relative content of CD44 in different strata and cell types of normal human epidermis. We found that CD44 existed almost exclusively on the plasma membranes; only rare labeling occurred on vesicular structures within the cytoplasm. Quantitation of the immunogold particles indicated that the labeling density of melanocytes corresponded to that of basal keratinocytes, and Langerhans cells displayed a labeling density of ∼10% that of the surrounding spinous cells. Among keratinocyte strata, the highest labeling density occurred on spinous cells, suggesting upregulation of CD44 after detachment from the basement membrane. The plasma membrane distribution of CD44 was compartmentalized, with little signal on cell–cell and cell-substratum contact sites such as desmosomes, the plasma membrane domain facing the basement membrane, and the close apposition of terminally differentiating granular cells. In contrast, CD44 was abundant on plasma membrane domains facing an open intercellular space, rich in hyaluronan. This distribution is in line with a role of CD44 as a hyaluronan receptor, important in the maintenance of the intercellular space for nutritional and cell motility functions in stratified epithelia.


Author(s):  
Michael Edidin

Cell surface membranes are based on a fluid lipid bilayer and models of the membranes' organization have emphasised the possibilities for lateral motion of membrane lipids and proteins within the bilayer. Two recent trends in cell and membrane biology make us consider ways in which membrane organization works against its inherent fluidity, localizing both lipids and proteins into discrete domains. There is evidence for such domains, even in cells without obvious morphological polarity and organization [Table 1]. Cells that are morphologically polarised, for example epithelial cells, raise the issue of membrane domains in an accute form.The technique of fluorescence photobleaching and recovery, FPR, was developed to measure lateral diffusion of membrane components. It has also proven to be a powerful tool for the analysis of constraints to lateral mobility. FPR resolves several sorts of membrane domains, all on the micrometer scale, in several different cell types.


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