Many cells secrete proteins into their surrounding extracellular fluid. Some cells, for example, secrete regulatory molecules such as hormones and neurotransmitters. Others release digestive enzymes, antibodies, or mucus. And throughout the body, cells such as fibroblasts secrete collagen and other structural proteins to provide strength and hold the body together.
All proteins, whether they are used in a cell or secreted, are synthesized at cellular structures called ribosomes. If the protein is to be used with the cell, the ribosome remains in the cytosol and the completed protein is released into the cytosol. But if a protein is destined for secretion, the very first amino acids in the polypeptide chain are a special sequence called the signal sequence. Shortly after the synthesis of this sequence is completed, the synthesis stops until the ribosome docks at the rough endoplasmic reticulum.
Once docked, the synthesis continues, with the new protein threading into the rough endoplasmic reticulum. The signal sequence is then cleaved from the polypeptide chain. Often, too, further enzymes cut the protein in other places. Most secreted proteins are modified before secretion.
Next, vesicles containing the protein bud from the rough endoplasmic reticulum and move too nearby the nearby Golgi apparatus. This is comprised of a stack of large, flattened vesicles. It is often likened to a stack of pita breads. The vesicles from the rough endoplasmic reticulum fuse with one end, adding their proteins to the first flattened vesicle. In turn, small vesicles bud from this structure and transfer the protein to the next layer of the stack. This continues until the protein winds up at the opposite end of the Golgi apparatus.
Once the protein has moved through the entire Golgi apparatus, secretion vesicles containing the protein bud off. These vesicles move to the plasma membrane, attach to the membrane, and then release their contents into the extracellular fluid through the process of exocytosis. Often a signal is required to initiate the release.
Collagen is a secreted protein we will encounter frequently, especially in lab. It is the most abundant protein in the body. A tendon, for example, is almost entirely collagen. And it is abundant in skin, bone and indeed in extracellular spaces throughout the body, where it holds the cells of the body together. A fibroblast is often the cell making the collagen.
The figure to the right is from an earlier webpage and shows a small segment of the molecule. The center portion of the molecule is a repetition of a dozens of segments exactly like this. As you can see, the molecule consists of three polypeptide chains. The tightly packed structure makes the center of the molecule stiff and linear.
During the synthesis, the three chains are synthesized separately, and then, of course, the signal sequences are removed. Next, while still in the endoplasmic reticulum, the three polypeptide chains wind around each other into the quaternary structure shown. However, only the central portion of each polypeptide chain forms this stiff, rod-like structure. Both ends of each polypeptide chain have a very different amino acid composition. Thus the initial quaternary structure consists of a long rod-like structure in the middle with a tangled region on each end. This structure is called procollagen and is relatively soluble. This is important because if the molecules aggregated inside the cell, it doubtless would be fatal to the cell.
The procollagen undergoes some further modification and then is secreted from secretion vesicles into a groove at the surface of the cell. There procollagen proteinases cleave off the tangled portions of the molecules at the ends. The resulting straight molecule is called tropocollagen and is far less soluble. For this reason, the tropocollagen molecules begin adhering to one another in the groove to form a fibril, which is spun out of the groove. The molecules are further modified with crosslinks to lock together into extremely strong fibers that are largely responsible for holding the body together.
(As you will learn in lab, there are actually several major categories of collagen -- types I, II, III, and IV. These each play different roles.)
As many proteins move through the rough ER and Golgi apparatus, they have carbohydrate added to them so that they become glycoproteins. While some glycosylation occurs in the rough ER, most often it takes place in the Golgi apparatus. Glycosylation makes the secreted protein much more polar, which contributes to its solubility and stability. Growth hormone, for example, is a protein with some carbohydrate added for this reason.
But some secreted proteins are heavily glycosylated in order to take up and hold much water. Mucus is an example of heavily glycosylated proteins in which the glycosylation creates the characteristic physical properties of the substance.
Another important type of heavily glycosylated protein that we will encounter periodically are the proteoglycans. The type of carbohydrate added to this class of glycoproteins are the glycoaminoglycans (GAGs). The monosaccharides in this special type of carbohydrate assemble into linear chains, (unlike glucose, which forms the heavily branched structure of glycogen).
Proteoglycans have the GAGs attached to the protein that runs along the core of the molecule. The resulting structure often looks somewhat like the brush used to clean test tubes, with the linear GAGs arranged like the bristles that project outward from the central core. The GAGs have many negative charges.
The figure to the right shows a simple proteoglycan. Many such molecules often aggregate into huge complexes by binding to a further long linear molecule (such as hyaluronan).
Proteoglycans take up much water and are abundant in the fluid between cells, which is called interstitial fluid. The proteoglycans make the interstitial fluid more gel-like than fluid.
Cartilage contains a large amount of proteoglycan aggregates. By themselves, proteoglycans would create an extremely weak, soluble structure. The strength and toughness of cartilage is provided by collagen. But collagen by itself has the properties of tendons or the dermis of the skin. Adding the heavily glycosylated proteoglycans provides the characteristic shock absorbing property, which is extremely important in the intervertebral discs between the vertebrae. The proteoglycans also give a "springiness" to cartilage. Find an extremely friendly (and smaller) person and tweak his or her nose. Notice how it springs back. Try it again. This is the contribution that the proteoglycans add when combined with collagen.
QUESTION: How do newly synthesized membrane proteins wind up embedded in the plasma membrane?
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In many important physiological processes, membrane proteins are removed from the plasma membrane and then returned in a relatively short time. Membrane proteins are removed from the plasma membrane through the formation of vesicles by endocytosis. Inside the cell, these vesicles fuse with a larger, membranous structure called an endosome. Vesicles budding from the endosome can then fuse with the plasma membrane, adding the proteins once again to the plasma membrane. Endosomes are a quick means of forming new secretion vesicles.