Hepatocytes secrete proteins into circulation via transport in vesicles and exocytosis. Protein synthesis begins with transcription of DNA to mRNA in the nucleus. mRNA is then translated into protein by membrane-bound ribosomes on the rough endoplasmic reticulum. The proteins are packaged into vesicles in the Golgi apparatus and transported to the cell membrane, where they are released via exocytosis into circulation.

1. PROTEIN SECRETION BY
HEPATOCYTES
Danny Taheri
Linda Amo-Mensah
Vishal Kinkhabwala
Andrea Whitley

2. THE QUESTION:
• Beginning with protein synthesis in
membrane-bound ribosomes, hepatocytes
secrete proteins into the circulation via which
of the following mechanisms?
•
•
•
•
•
A: Active transport through the cell membrane
B: Diffusion through the cell membrane
C: Transport by microtubules and exocytosis
D: Transport in vesicles and exocytosis
E: Transport through pores in the cell membrane

3. PROTEIN SYNTHESIS AND SECRETION
• Central Dogma of
Biology: DNA  mRNA
 PROTEIN
• DNA is transcribed into
mRNA in the nucleus
• mRNA is then
TRANSLATED into a
protein by the
ribosomes in the
cytoplasm

4. TRANSLATION
• The mRNA is translated
into protein in the
ribosome through the
action of adding Amino
Acids to make a
polypeptide
• These ribosomes can
either be Free Polysomes
in the cytoplasm, or
Membrane-Bound
Ribosomes, attached to
the Rough Endoplasmic
Reticulum

5. Post-Translational Modification
• The polypeptide is then
released into the
cytoplasm, ready for posttranslational
modifications
• The proteins then enter
the Golgi Apparatus,
where they are packaged
into vesicles, which then
move to the plasma
membrane, where they
are released into
circulation

6. Free vs. Membrane-Bound Ribosomes
• FREE:
• Proteins formed from
free ribosomes, are
released into the
cytosol and used within
the cells
• They are moved about
anywhere in the cytosol
but are excluded from
the cell nucleus.

7. Free vs. Membrane-Bound Ribosomes
• MEMBRANOUS
• They are attached to the cell
and synthesize proteins in the
membranous cell organelles
• The organelles they bound to
are rough endoplasmic
reticulum.
• The newly produced
polypeptide chains are
inserted direct into the rough
endoplasmic reticulum by the
ribosome undertaking
vectorial synthesis and are
then transported to their
various destinations through
the secretory pathways.
• Bound ribosomes usually
produce proteins that are used
within the plasma membrane
or are expelled from the cell
via exocytosis

8. HEPATOCYTES
• Primary cell type in the
liver
• One major function is
synthesis and secretion
of Plasma Proteins

9. SECRETED PROTEINS
• 1. Albumin: Maintains
osmotic pressure
• 2. Alpha-Fetoprotein:
High levels detected in
congenital anomalies
(i.e. spina bifida)
• 3. C-Reactive Protein:
Major role in
inflammatory response
• 4. Transferrin: Transfers
iron from duodenum to
body tissues

10. SECRETED PROTEINS
• 5. Plasminogen:
• Thrombolitic – breaks
down clots
• Active form of Plasmin
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•
•
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6. Clotting Factors
Most important:
CF 1: Fibrinogen
CF 2: Prothrombin

11. BACK TO THE QUESTION
• Beginning with protein synthesis in membranebound ribosomes, hepatocytes secrete proteins
into the circulation via which of the following
mechanisms?
• A: Active transport through the cell membrane
• B: Diffusion through the cell membrane
• C: Transport by microtubules and exocytosis
• D: Transport in vesicles and exocytosis
• E: Transport through pores in the cell membrane

12. A: Active Transport through the Cell
Membrane
• WHY It Could Be:
• Proteins would have to cross through a cell membrane to exit
the cell (Wang and Boyer, 2004)
• ATP (is a component of active transport) is often a component
of protein secretion (Chen and Tai, 1985)
• WHY It Isn’t:
• Movement through the Golgi Apparatus would involve
vesicles, and active transport does not use vesicles
• No gradients or pumps  No Active Transport used (Wang
and Boyer, 2004)

13. B: Diffusion through the Cell
Membrane
• WHY It Could Be:
• Proteins would need to cross cell membrane to exit cell
• WHY It Isn’t:
• Passive Diffusion is not possible due to the polar nature of
proteins and their inability to freely cross the phospholipid
bilayer (Wang and Boyer, 2004)

14. C: Transport by Microtubules and
Exocytosis
• WHY It could be:
• Exocytosis (through vesicles) is a MAJOR component of
protein secretion
• WHY It isn’t:
• NO use of microtubules seen in this process (Wang and Boyer,
2004)

15. E: Transport through Pores in the Cell
Membrane
• WHY It could be:
• Release of certain substances from a cell does move through
pores
• WHY It isn’t:
• Protein synthesis and secretion does not usually go through
pores but rather bud off through membrane vesicles (Wang
and Boyer, 2004)

16. D: Transport in Vesicles and
Exocytosis
• WHY It Is:
• Proteins are packaged into vesicles and then released from
the membrane via exocytosis (Wang and Boyer, 2004)
• Consistent with examination of the overall process!

17. References
• Boron, W. F., & Boulpaep, E. L. (2009). Uptake, Processing, &
Secretion of Compounds by Hepatocytes. In Medical physiology: A
cellular and molecular approach. Philadelphia, PA:
Saunders/Elsevier.
• Chen, L., & Tai, P. (1985). ATP is essential for protein translocation
into Escherichia coli membrane vesicles. Proceedings of the
National Academy of Science, 82, 4384-4388.
• University of Washington (2012). Cell Secretion. Retrieved from
http://courses.washington.edu/conj/cell/secretion.htm
• Wang, L., & Boyer, J. (2004). The Maintenance and Generation of
Membrane Polarity in Hepatocytes. Science Frontier, 39(4), 892899.