Introduction to the Human Cell. Danton PhD O'Day
targeted to specific cell types. One goal is to find or develop specific liposomal proteins that can seek out cancer cells where they can bind and fuse with them to transport chemotherapeutic or other agents into those cells to destroy them. As another example, liposomes can also be used to transfer genes or enzymes into cells to correct for the absence of specific proteins. This is being done today to treat various diseases as detailed later in this book.
Cholesterol: Stabilizes the Membrane
As mentioned above, cholesterol is found at high levels in the cell membrane and to a lesser degree in intracellular membranes. It is a steroid lipid that is also involved in the synthesis of sex hormones but here we’re interested in why it localizes to the cell membrane. As shown in the following figure (Figure 2.5, left side), cholesterol has a flat shape: The planar steroid ring structure allows it to interdigitate between phospholipids (Figure 2.5, right side). It is present in animal and human cell membranes to give stability and rigidity.
Figure 2.5. The structure of cholesterol and its ability to interdigitate between phospholipids in the cell membrane.
The more cholesterol there is the more rigid and inflexible the membrane becomes. As a result, depending on the cell type and its location and function, it will contain different amounts of cholesterol in its cell membrane. There is little cholesterol in cytoplasmic organelle membranes because they need to be flexible and aren’t subjected to events that can disrupt them. Cholesterol is absent from bacteria and most plants where cell walls provide stability and protection.
Membrane Protein Functions
As you will begin to realize as you progress through this book, there are thousands of different membrane proteins. These proteins serve a diverse number of functions.
In future chapters we will do the following to elaborate the attributes of membrane proteins:
•Define their functions (e.g., cell adhesion, intercellular communication)
•Characterize various types including enzymes, channels, adhesion molecules
•Show that some proteins float freely in the lipid bilayer
•Show many proteins are attached to the cytoskeleton
•Reveal that the types of membrane proteins are also classified based upon isolation techniques as integral or peripheral
Association of Proteins with the Cell Membrane
Membrane proteins associate with the lipid bilayer in many different ways. This has to do with their functions as well as their structure. The figure below shows the most common liaisons that occur (Figure 2.6).
Figure 2.6. The various ways proteins can associate with the cell membrane.
Thus membrane proteins can associate with the inside only, the outside only or they may pass right through the membrane. In the latter case, some proteins contain a single lipid-spanning domain (single pass) while others have several (multipass). Proteins may be linked to the membrane by a glycolipid or phospholipid anchor. Proteins that are linked to or embedded in the cell membrane may associate with other proteins (protein-protein interactions) either on the inner or outer face of the membrane. Proteins can also interact directly with lipids in the bilayer. Specific examples of each of these associations will be discussed in subsequent chapters.
Glycoproteins Sugar Coat the Cell
While human cells don’t have a cell wall, they do have a sugar coating! Many membrane proteins are covalently linked to sugar residues. The residues may consist of a few sugars or they may extend into long carbohydrate moieties. The sugar groups in membrane proteins, as well as in glycolipids, always orient towards the external environment. They always orient outside the cell, never towards the cytoplasm. The following figure shows an example of an integral membrane glycoprotein (Figure 2.7).
Figure 2.7. The basic structure of a typical glycoprotein and its association with the cell membrane.
When the carbohydrate component of the glycoprotein is extensive, typically interacting with extracellular matrix components, it can be seen in the electron microscope. For example, the extensive “sugar coating” of the intestinal epithelium is called the glycocalyx (Figure 2.8). The extensive glycocalyx in the intestine protects against injury, bacterial infections and aids in absorption of nutrients. Some use the term glycocalyx more loosely to mean the surface carbohydrate component of all cells and not just the extensive coating exemplified by intestinal epithelial cells.
Figure 2.8. The glycocalyx of intestinal epithelial cell membranes.
Protein Domains in Cell Membranes
In most cells, the membrane proteins are not randomly localized but exist in complexes that are localized to specific domains. This fits well into our idea that the cell membrane is a fluid “mosaic” model. One of the first cell types where protein membrane domains were identified was the sperm cell as shown in the next figure (Figure 2.9). Sperm components were injected into rabbits to induce antibody formation. Three rabbit antibodies that were produced identified three different regions of the surface (i.e., proteins in the membrane) of the sperm. Before we look at these results in detail, let’s look at the structure of the human sperm cell.
Each of the components of the sperm has a specific function. Their overall job is to get their payload, the haploid male nucleus, into the egg cytoplasm where it can fuse with the female pronucleus to form the diploid, zygote nucleus.
Figure 2.9. The structure of the human sperm cell.
Thus it is clear that each region of the sperm has a specific function. That said, it would also be expected that each of the regions has specific, unique proteins associated with it. However, conjecture in science is of no value without experimentation. So the following experiments were critical to validating these ideas or, if we can be more bold, hypotheses.
Figure 2.10. Fractions of the human sperm cell were injected into rabbits to make polyclonal antibodies which were then used to stain sperm. This revealed that different proteins were localized in different regions of the sperm cell.
This work showed:
•Some proteins are restricted to certain locations
•Each region (acrosome, nucleus, tail) has specific proteins associated with it
•These proteins are not found in the other regions (i.e., they are region-specific)
•It's common for specific regions to serve special functions (e.g. sperm's receptor for egg binding and fusion; junctional adhesion molecules)
The way specific proteins localize and also form complex protein domains is an exciting area of cell biology that is growing rapidly. For example, RACK1 (Receptor for Activated C Kinase 1) organizes many constituents involved in cellular signaling as covered in a future chapter.
Lipid