Introduction to the Human Cell. Danton PhD O'Day

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СКАЧАТЬ define many of the functional aspects of membranes

      •Some membranes are designed for fusion: e.g., sperm-egg, myoblasts

      •Specificity of fusion is defined by membrane proteins

      Looking Ahead

      Throughout this book we will touch upon all of the topics covered in this chapter and how they apply to specific diseases. We will look at how membrane proteins mediate not only cell adhesion but how cells communicate with each other to regulate their behavior. We’ll see how these interactions change in cancer cells as well. While we won’t be focusing on the carbohydrates and lipids as much as proteins, they are still critical to many of the topics that we will cover. They are also important to cell structure and function as a whole and in the disease process.

      Chapter 3

      Junctional Adhesion Complexes: Mobile Proteins and Bacterial Mimics

      The evolution of higher organisms required that single cells first formed multicellular associations. Once this was accomplished individual cells or groups of cells could then specialize for specific functions. Ultimately the evolution of tissues and organs was possible. It is likely that this all began with the first cell adhesion molecules that allowed two cells to stick together for reproduction. Over time, new adhesion molecules evolved and the link between them and the intracellular environment began to appear ultimately leading to the formation of fully-fledged adhesion junctions found in human tissues. This theoretical model for the evolution of cell adhesion junctions is summarized in the following figure (Figure 3.1).

      Figure 3.1. A theoretical model for the evolution of cell adhesion junctions.

      In its simplest form, cell adhesion involves two identical molecules: homotypic cell adhesion. Binding between two different cell adhesion molecules is called heterotypic cell adhesion. These two simplest associations, as well as some others discussed in the next chapter, led to the next step in cell adhesion mechanisms: clustering of cell adhesion molecules to form more complex adhesion structures. Today, these are seen as the highly organized adhesion junctions that consist of cell adhesion molecules as well as accessory and adaptor proteins that allow other interactions including links to the intracellular cytoskeleton and the extracellular matrix.

      In this chapter, we will examine the major junctions that are found in human tissues and some of the diseases that are related to their structure and function. Later, we'll look in detail at some of the cell adhesion molecules that are present in these junctions, some of which also work independently.

      Cell Adhesion Mechanisms

      The following diagram shows that cells can adhere via various mechanisms (Figure 3.2). Many of these cell adhesions mediate other cellular functions, as we will see throughout this volume. The image that is shown is based on the organization of junctional adhesion complexes that are seen in the human gut.

      Figure 3.2. The localization and components of cell adhesion junctions in intestinal epithelial cells.

      Cells adhere to each other via:

      •Junctional adhesion mechanisms (tight junctions, adherens junctions, desmosomes, gap junctions)

      •Cell adhesion molecules (next chapter)

      Cells adhere to the substratum, basal lamina or extracellular matrix via:

      •Hemidesmosomes

      •Focal contacts (detailed in later chapters)

      •Integrins (detailed in later chapters)

      •Integral membrane proteoglycans (summarized in a later chapter)

      As shown in the following figure, groups of junctions including tight and adherens junctions and desmosomes make up junctional adhesion complexes as seen in epithelial and cardiac tissues (Figure 3.3). These junctional adhesion complexes provide strong binding between these cells that are often subjected to great stresses. They also mediate intercellular communication and play a critical role in cell polarity. Links to the cytoskeleton (actin, keratin) are also present. The following transmission electron microscope photo shows the junctional adhesion complex present in the apical region of the intestinal mucosa (Figure 3.3).

      Figure 3.3. An ultrastructural image of the localization of cell adhesion junctions in intestinal epithelial cells.

      Junctional Adhesion Molecules

      Cell junctions are made up of many proteins with diverse functions. Often Junctional Adhesion Molecules (JAMs) are related to other protein isoforms or variants that appear in other contexts (e.g., cadherins and integrins function as JAMs and as individual cell adhesion molecules). In contrast, some junctions contain unique proteins (e.g., connexin proteins of gap junctions).

      In the following figure, notice that cadherins are involved in cell-cell adhesion as part of desmosomes and adherens junctions while integrins mediate cell-substratum adhesions via hemi-desmosomes and focal adhesions (Figure 3.4). As discussed in the next chapter, cadherins and integrins are also cell adhesion molecules that function independently from their role in cell junctions. Thus certain proteins can serve dual or even multiple functions in a cell. More often than not, the specific cell adhesion proteins (e.g., cadherins, integrins) are variant proteins either coded for by another gene or resulting from post-translational modifications once the gene has been transcribed as will be covered in the next chapter.

      Figure 3.4. Types of cell and junctional adhesion proteins.

      Tight Junctions

      The tight junction was first resolved in the electron microscope as tightly associated regions between the cell membranes of adjacent cells. Tight junctions are also known as “occluding junctions” or “zonula occludens.” They prevent the flow of water and molecules between cells, thus restricting them from exiting the extracellular environment to penetrate the intercellular space. This is called “paracellular movement.”

      Tight junctions serve another critical role because they also prevent the movement of membrane components between the top (apical) and bottom (basal) sides of the cell. Thus they serve to restrict protein movements that would otherwise be possible because of the fluidity of the cell membrane. Restricting where certain proteins are localized is a critical event in establishing the polarity of cells. In the example used here, the tight junctions clearly define where the microvilli can form (i.e., apical) versus the cell’s interaction with and adhesion to the basement membrane (i.e., basal).

      Figure СКАЧАТЬ