1. Protein Secretion Sarah Thomas

2. Secretory Pathway n Ribosomes that are synthesizing proteins and bear an ER signal sequence bind to rough ER. n Once transcription is complete, the polypeptide chains can: –be inserted into the ER membrane OR –cross the ER membrane and go into the lumen

3. n Some will remain in the ER and others will move on to be secreted. n The proteins that are destined to be secreted will move into transport vesicles. n Transport vesicles are “buds” from the ER. n These transport vesicles will fuse together to form the cis-Golgi reticulum. n This will physically move “upward” to cis- Golgi, to medial-Golgi, to trans-Golgi, and finally to trans-Golgi reticulum.

4. n During this movement, the proteins are folded, modified, and given an “address” (attach oligosaccharides). n Some ER-localized proteins go back to the ER via retrograde Golgi-to-ER transport. n Others will undergo retrograde transport from later to earlier Golgi. n From the trans-Golgi reticulum, the protein is sorted into one of two types of vesicles:

5. –Transport vesicle: -In these vesicles, proteins are secreted continuously (constitutive secretion). This occurs in all cells. Examples are secretion of collagen by fibroblasts and serum proteins by hepatocytes. –Secretory vesicle: -In these vesicles, proteins are only secreted once the cell has received a neural or hormonal signal releasing them (regulated secretion). This only occurs in some cells. Examples are secretion of precursors of digestive enzymes by pancreatic cells and hormones by endocrine cells.

6. Hepatocytes n Hepatocytes are liver cells. n Hepatocytes are used in many experiments to study the protein secretion pathway. n These cells are rich in organelles. They have lots of mitochondria, ribosomes, lysosomes, and especially Golgi bodies and endoplasmic reticulum. n They also have large amounts of stored glycogen and can have more than one nucleus (commonly two full-size nuclei)

7. n Hepatocytes: –form and secrete bile –store glycogen and buffer blood glucose –synthesize urea –metabolize cholesterol and fat –synthesize plasma proteins –detoxify many drugs and other poisons –process several steroid hormones and vitamin D –produce blood clotting factors

8. n Hepatocytes account for approximately 90% of the liver’s volume. n The liver is responsible for the synthesis and secretion of most blood proteins (except antibodies). n The most abundant serum protein secreted is albumin. If the liver is impared, there are decreased amounts of serum albumin, this may cause edema.

9. n The liver also produces most of the proteins responsible for blood clotting (coagulation or clotting factors). If there is a decrease in production of these factors, excessive bleeding may result. n Bile is also synthesized by hepatocytes and secreted into biliary ducts. From there it leaves the liver to be temporarily stored in the gallbladder before emptying into the small intestine.

10. n Liver damage or obstruction of a bile duct can lead to the blockage of bile flow, which causes the malabsorption of dietary fats, four-smelling diarrhea caused by non-absorbed fats, and jaundice.

11. Causes of Damage and Death of Hepatocytes n Disease n Traumatic injury n Viral hepatitis n Drugs n Alcohol

12. Summary n Proteins are synthesized and secreted starting with the rough ER, going through the Golgi bodies, and to their destination via transport or secretory vesicles. n Secretory vesicles are those, that upon a neural or hormonal signal, will release the protein (regulated secretion). n Transport vesicles are those that continuously secrete proteins (constitutive secretion). n Hepatocytes are vital for the proper function of the liver. They synthesize and secrete many proteins in the body and are used for protein secretion experiments.

13. Questions???