Ganong's Review of Medical Physiology, 23rd Edition

CHAPTER 2

Overview of Cellular Physiology in Medical Physiology 37

receptors and form
focal adhesion complexes,
which serve as
points of traction with the surface over which the cell pulls itself.
In addition, some molecular motors use microfilaments as tracks.

MOLECULAR MOTORS

The molecular motors that move proteins, organelles, and
other cell parts (collectively referred to as “cargo”) to all parts
of the cell are 100 to 500 kDa ATPases. They attach to their
cargo at one end of the molecule and to microtubules or actin
polymers with the other end, sometimes referred to as the
“head.” They convert the energy of ATP into movement along
the cytoskeleton, taking their cargo with them. There are three
super families of molecular motors:
kinesin, dynein,
and
my-
osin.
Examples of individual proteins from each superfamily
are shown in Figure 2–7. It is important to note that there is
extensive variation among superfamily members, allowing for
specialization of function (eg, choice of cargo, cytoskeletal fil-
ament type, and/or direction of movement).
The conventional form of
kinesin
is a doubleheaded mole-
cule that tends to move its cargo toward the “+” ends of
microtubules. One head binds to the microtubule and then
bends its neck while the other head swings forward and binds,
producing almost continuous movement. Some kinesins are
associated with mitosis and meiosis. Other kinesins perform
different functions, including, in some instances, moving cargo
to the “–” end of microtubules.
Dyneins
have two heads, with
their neck pieces embedded in a complex of proteins.
Cyto-
plasmic dyneins
have a function like that of conventional
kinesin, except they tend to move particles and membranes to
the “–” end of the microtubules. The multiple forms of
myo-
sin
in the body are divided into 18 classes. The heads of myo-
sin molecules bind to actin and produce motion by bending
their neck regions (myosin II) or walking along microfila-
ments, one head after the other (myosin V). In these ways,

they perform functions as diverse as contraction of muscle

and cell migration.

CENTROSOMES

Near the nucleus in the cytoplasm of eukaryotic animal cells is a

centrosome.

The centrosome is made up of two

centrioles

and

surrounding amorphous

pericentriolar material.

The centri-

oles are short cylinders arranged so that they are at right angles

to each other. Microtubules in groups of three run longitudinally

in the walls of each centriole (Figure 2–1). Nine of these triplets

are spaced at regular intervals around the circumference.

The centrosomes are

microtubule-organizing centers

(MTOCs)

that contain

γ

-tubulin. The microtubules grow out

of this

γ

-tubulin in the pericentriolar material. When a cell

divides, the centrosomes duplicate themselves, and the pairs

move apart to the poles of the mitotic spindle, where they

monitor the steps in cell division. In multinucleate cells, a

centrosome is near each nucleus.

CILIA

Cilia

are specialized cellular projections that are used by unicellu-

lar organisms to propel themselves through liquid and by multi-

cellular organisms to propel mucus and other substances over the

surface of various epithelia. Cilia are functionally indistinct from

the eukaryotic flagella of sperm cells. Within the cilium there is an

axoneme

that comprises a unique arrangement of nine outer mi-

crotubule doublets and two inner microtubules (“9+2” arrange-

ment). Along this cytoskeleton

is

axonemal dynein.

Coordinated

dynein-microtubule interactions within the axoneme are the ba-

sis of ciliary and sperm movement. At the base of the axoneme

and just inside lies the

basal body.

It has nine circumferential

triplet microtubules, like a centriole, and there is evidence that

basal bodies and centrioles are interconvertible.

FIGURE 2–7
Three examples of molecular motors.
Conventional kinesin is shown attached to cargo, in this case a membrane-bound organelle.
The way that myosin V “walks” along a microtubule is also shown. Note that the heads of the motors hydrolyze ATP and use the energy to produce motion.

Cytoplasmic dynein

4 nm

Cargo

Light

chains

80 nm

Conventional kinesin

Cargo-binding domain

Head 1 Head 2 Head 2 Head 1

Actin

ADP ADP ATP

Myosin V