Ganong's Review of Medical Physiology, 23rd Edition

42 SECTION ICellular & Molecular Basis of Medical Physiology

The Golgi apparatus is a polarized structure, with cis and
trans sides (Figure 2–11). Membranous vesicles containing
newly synthesized proteins bud off from the granular endo-
plasmic reticulum and fuse with the cistern on the cis side of
the apparatus. The proteins are then passed via other vesicles
to the middle cisterns and finally to the cistern on the trans
side, from which vesicles branch off into the cytoplasm. From
the trans Golgi, vesicles shuttle to the lysosomes and to the
cell exterior via constitutive and nonconstitutive pathways,
both involving exocytosis. Conversely, vesicles are pinched
off from the cell membrane by endocytosis and pass to endo-
somes. From there, they are recycled.
Vesicular traffic in the Golgi, and between other membra-
nous compartments in the cell, is regulated by a combination
of common mechanisms along with special mechanisms that
determine where inside the cell they will go. One prominent
feature is the involvement of a series of regulatory proteins
controlled by GTP or GDP binding (small G proteins) associ-
ated with vesicle assembly and delivery. A second prominent
feature is the presence of proteins called SNAREs (for solu-
ble N-ethylmaleimide-sensitive factor attachment receptor).
The v- (for vesicle) SNAREs on vesicle membranes interact in
a lock-and-key fashion with t- (for target) SNAREs. Individual
vesicles also contain structural protein or lipids in their mem-
brane that help to target them for specific membrane compart-
ments (eg, Golgi sacs, cell membranes).

QUALITY CONTROL

The processes involved in protein synthesis, folding, and migra-
tion to the various parts of the cell are so complex that it is re-
markable that more errors and abnormalities do not occur. The
fact that these processes work as well as they do is because of
mechanisms at each level that are responsible for “quality con-
trol.” Damaged DNA is detected and repaired or bypassed. The
various RNAs are also checked during the translation process.
Finally, when the protein chains are in the endoplasmic reticu-

lum and Golgi apparatus, defective structures are detected and

the abnormal proteins are degraded in lysosomes and protea-

somes. The net result is a remarkable accuracy in the produc-

tion of the proteins needed for normal body function.

APOPTOSIS

In addition to dividing and growing under genetic control, cells

can die and be absorbed under genetic control. This process is

called programmed cell death, or apoptosis (Gr. apo “away” +

ptosis “fall”). It can be called “cell suicide” in the sense that the

cell’s own genes play an active role in its demise. It should be

distinguished from necrosis (“cell murder”), in which healthy

cells are destroyed by external processes such as inflammation.

Apoptosis is a very common process during development

and in adulthood. In the central nervous system, large numbers

of neurons are produced and then die during the remodeling

that occurs during development and synapse formation. In the

immune system, apoptosis gets rid of inappropriate clones of

immunocytes and is responsible for the lytic effects of gluco-

corticoids on lymphocytes. Apoptosis is also an important fac-

tor in processes such as removal of the webs between the

fingers in fetal life and regression of duct systems in the course

of sexual development in the fetus. In adults, it participates in

the cyclic breakdown of the endometrium that leads to men-

struation. In epithelia, cells that lose their connections to the

basal lamina and neighboring cells undergo apoptosis. This is

responsible for the death of the enterocytes sloughed off the tips

of intestinal villi. Abnormal apoptosis probably occurs in

autoimmune diseases, neurodegenerative diseases, and cancer.

It is interesting that apoptosis occurs in invertebrates, including

nematodes and insects. However, its molecular mechanism is

much more complex than that in vertebrates.

One final common pathway bringing about apoptosis is acti-

vation of caspases, a group of cysteine proteases. Many of these

have been characterized to date in mammals; 11 have been

found in humans. They exist in cells as inactive proenzymes

FIGURE 2–11 Cellular structures involved in protein processing. See text for details.

Nucleus Lysosome Late endosome Early endosome

Regulated secretion

Constitutive

secretion

Endocytosis

Recycling

ER Golgi apparatus Secretory granules