Chapter 17 Cytoskeleton

cytoskeleton

• an intricate network of protein filaments that extends throughout the cytoplasm

• is most prominent in the large and structurally complex eukaryotic cell

• controls the location of the organelles and provides the machinery for transport between them

• also responsible for the segregation of chromosomes into two daughter cells at cell division and for pinching apart those two new cells

intermediate filaments, microtubules, and actin filaments

The cytoskeleton is built on a framework of three types of protein filaments:

fibrous; globular tubulin subunits; globular actin subunits

A family of — proteins forms the intermediate filaments; — form microtubules; and — form actin filaments

Intermediate filaments

• have great tensile strength, and their main function is to enable cells to withstand the mechanical stress that occurs when cells are stretched.

• are the toughest and most durable of the cytoskeletal filaments:

cytoplasm

Intermediate filaments are found in the — of most animal cells.

desmosomes

intermediate filaments are often anchored to the plasma membrane at cell–cell junctions called

nuclear lamina

Intermediate filaments are also found within the nucleus of all eukaryotic cells

α-helical region

The rod domain of intermediate filament consists of an extended —n that enables pairs of intermediate filament

staggered tetramer

Two of these coiled-coil dimers in intermediate filaments, running in opposite directions, associate to form a —

true

true or false.Because the two dimers point in opposite directions, the two ends of the tetramer are the same, as are the two ends of assembled intermediate filaments;

noncovalent

All the interactions between the intermediate filament proteins depend solely on — bonding;

it is the combined strength of the overlapping lateral interactions along the length of the proteins

gives intermediate filaments their great tensile strength.

(1) keratin filaments in epithelial cells;

(2) vimentin and vimentin-related filaments

; (3) neurofilaments in nerve cells; and

(4) nuclear lamins, which strengthen the nuclear envelope.

Intermediate filaments can be grouped into four classes

are the most diverse class of intermediate filament.

keratin filaments

are the most diverse class of intermediate filament.

desmosomes

The ends of the keratin filaments are anchored to the —, and the filaments associate laterally with other cell components through the globular head and tail domains that project from their surface.

epidermolysis bullosa simplex,

mutations in the keratin genes interfere with the formation of keratin filaments in the epidermis

plectin

I.F. that cross-link the filaments into bundles and link them to microtubules, to actin filaments, and to adhesive structures in the desmosomes

lamins

the intermediate filaments that form this tough nuclear lamina are constructed from a class of intermediate filament proteins called —

Dephosphorylation by protein phosphatases at the end of mitosis

causes the lamins to reassemble

progeria

—rare disorders that cause affected individuals to age prematurely

microtubules

• grow out from a small structure near the center of the cell called the centrosome

mitotic spindle.

• When a cell enters mitosis, the cytoplasmic microtubules disassemble and then reassemble into an intricate structure called

• provides the machinery that will segregate the chromosomes equally into the two daughter cells just before a cell divides

cilia and flagella

where are microtubules present

motor proteins

propel organelles along cytoskeletal tracks

tubulin

Microtubules are built from subunits called — which is itself a dimer composed of two very similar globular proteins

α-tubulin and β-tubulin

two very similar globular proteins that make up a tubulin

noncovalent interactions

α-tubulin and β-tubulin are bound by

13 parallel protofilaments

each a linear chain of tubulin dimers with α- and β-tubulin alternating along its length

β-tubulin end

is called its plus end

α-tubulin end

minus end.

true

true or false. In a concentrated solution of pure tubulin in a test tube, tubulin dimers will add to either end of a growing microtubule. However, they add more rapidly to the plus end than to the minus end

centrosome

• organizes an array of microtubules that radiates outward through the cytoplasm

centrioles

• The centrosome consists of a pair of

y-tubulin

the centrosome matrix includes hundreds of ringshaped structures formed from a special type of tubulin, called

γ-tubulin ring complex

serves as the starting point in centrosome

nucleation site

another name for the starting point of the growth of one microtubule

αβ-tubulin

dimers add to each γ-tubulin ring complex in a specific orientation, with the result that the minus end of each microtubule is embedded in the centrosome, and growth occurs only at the plus end that extends into the cytoplasm

centriole

is made of a cylindrical array of short microtubules

basal bodies

Centrioles do, however, act as the organizing centers for the microtubules in cilia and flagella, where they are called

it is much harder to start a new microtubule from scratch, by first assembling a ring of αβ-tubulin dimers, than it is to add such dimers to a preexisting γ-tubulin ring complex

Why do microtubules need nucleating sites such as those provided by the γ-tubulin rings in the centrosome?

dynamic instability

This remarkable behavior—switching back and forth between polymerization and depolymerization

tubulin dimers to hydrolyze GTP

The dynamic instability of microtubules stems from the intrinsic capacity of

true

true or false. β-tubulin, which hydrolyzes the GTP to GDP shortly after the dimer is added to a growing microtubule.

“GTP cap.”

the end of a rapidly growing microtubule is composed entirely of GTP-tubulin dimers, which form a

drug colchicine

which binds tightly to free tubulin dimers and prevents their polymerization into microtubules, the mitotic spindle rapidly disappears, and the cell stalls in the middle of mitosis, unable to partition the chromosomes into two groups.

drug Taxol

has the opposite effect. It binds tightly to microtubules and prevents them from losing subunits

microtubule-destabilizing antimitotic drugs

Because cancer cells divide in a less controlled way than do normal cells of the body, they can sometimes be killed preferentially by

colchicine, Taxol, vincristine, and vinblastine

examples of microtubule-destabilizing antimitotic drugs

polarized

one end of the cell is structurally or functionally different from the other

• In the nerve cell, for example, all the microtubules in the axon point in the same direction, with their plus ends toward the axon terminals; along these oriented tracks, the cell is able to transport organelles, membrane vesicles, and macromolecules—either from the cell body to the axon terminals or in the opposite direction

microtubule-associated proteins

stabilize microtubules against disassembly, for example, while others link microtubules to other cell components, including the other types of cytoskeletal filaments

saltatory

Mitochondria and the smaller membraneenclosed organelles and vesicles travel in small, jerky steps—moving for a short period, stopping, and then moving again

motor proteins

Saltatory movements can occur along either microtubules or actin filaments. In both cases, the movements are driven by —

• which use the energy derived from repeated cycles of ATP hydrolysis to travel steadily along the microtubule or actin filament in a single direction

kinesins and dyneins

The motor proteins that move along cytoplasmic microtubules, such as those in the axon of a nerve cell, belong to two families

kinesins

generally move toward the plus end of a microtubule

dyneins

move toward the minus end

true

true or false. Both kinesins and dyneins are generally dimers that have two globular ATP-binding heads and a single tail

head

s interact with microtubules in a stereospecific manner, so that the motor protein will attach to a microtubule in only one direction.

tail

of a motor protein generally binds stably to some cell component, such as a vesicle or an organelle, and thereby determines the type of cargo that the motor protein can transport

ATP-hydrolyzing (ATPase) activity

The globular heads of kinesin and dynein are enzymes with —-.

• This reaction provides the energy for driving a directed series of conformational changes in the head that enable it to move along the microtubule by a cycle of binding, release, and rebinding to the microtubule

Cytoplasmic dyneins

the Golgi membranes pull the Golgi apparatus along microtubules in the opposite direction, inward toward the nucleus

cilia

are hairlike structures about 0.25 μm in diameter, covered by plasma membrane, that extend from the surface of many kinds of eukaryotic cells;

basal body

each cilium contains a core of stable microtubules, arranged in a bundle, that grow from a cytoplasmic —, which serves as an organizing center

flagella

• that propel sperm and many protozoa are much like cilia in their internal structure but are usually very much longer.

• They are designed to move the entire cell, rather than moving fluid across the cell surface

A cross section through a cilium shows nine doublet microtubules arranged in a ring around a pair of single microtubules in cilia and flagella

difference between microtubules in cilia and flagella and microtubules in cytoplasm

ciliary dynein

The most important of the accessory proteins is the motor protein

• generates the bending motion of the core

primary cilium

Many animal cells that lack beating cilia contain a single, nonmotile

Actin filaments

polymers of the protein actin, are present in all eukaryotic cells and are essential for many of the cell’s movements, especially those involving the cell surface.

actin-binding proteins

Actin filaments interact with a large number of — that enable the filaments to serve a variety of functions in cells.

myosin

Actin-dependent movements usually require actin’s association with a motor protein called

true

true or false. Although actin filaments can grow by the addition of actin monomers at either end, like microtubules, their rate of growth is faster at the plus end than at the minus end

hydrolysis of ATP to ADP

— in an actin filament reduces the strength of binding between the monomers in actin filaments, thereby decreasing the stability of the polymer

grow rapidly

If the concentration of free actin monomers is very high, an actin filament will —, adding monomers at both ends

treadmilling

• involves a simultaneous gain of monomers at the plus end of an actin filament and loss at the minus end: when the rates of addition and loss are equal, the filament remains the same size

true

true or false. Both the treadmilling of actin filaments and the dynamic instability of microtubules rely on the hydrolysis of a bound nucleoside triphosphate to regulate the length of the polymer.

Dynamic instability

• involves a rapid switch from growth to shrinkage (or from shrinkage to growth) at only the plus end of the microtubule.

5%

how many percent of the total protein in a typical animal cell is actin

thymosin and profilin

small proteins in cells that bind to actin monomers in the cytosol, preventing them from adding to the ends of actin filaments.

formins and actin-related proteins (ARPs)

When actin filaments are needed, other actin-binding proteins such as —promote actin polymerization

actin-binding proteins

hold actin filaments together in parallel bundles in microvilli; others cross-link actin filaments together in a gel-like meshwork within the cell cortex—the specialized layer of actin-filament-rich

cell cortex

actin filaments are linked by actin-binding proteins into a meshwork that supports the plasma membrane and gives it mechanical strength.

neutrophils

migrate out of the blood into infected tissues when they “smell” small molecules released by bacteria, which the neutrophils seek out and destroy

(1) the cell pushes out protrusions at its “front,” or leading edge;

(2) these protrusions adhere to the surface over which the cell is crawling; and

(3) the rest of the cell drags itself forward by traction on these anchorage points

3 mechanisms of Cell Crawling

lamellipodia

which contain a dense meshwork of actin filaments, oriented so that most of the filaments have their plus ends close to the plasma membrane

filopodia

• Many cells also extend thin, stiff protrusions, both at the leading edge and elsewhere on their surface

• These are about 0.1 μm wide and 5–10 μm long, and each contains a loose bundle of 10–20 actin filaments, again oriented with their plus ends pointing outward.

formins

• a nucleating protein that attaches to the growing plus ends of actin filaments and promotes the addition of new monomers to form straight, unbranched filaments.

• are also used elsewhere to assemble unbranched filaments, as in the contractile ring that pinches a dividing animal cell in two.

integrins

When the lamellipodia and filopodia touch down on a favorable surface, they stick: transmembrane proteins in their plasma membrane

myosin

All actin-dependent motor proteins belong to the — family

• bind to and hydrolyze ATP, which provides the energy for their movement along actin filaments toward the plus end

Myosin I

• present in all types of cells,

• have a head domain and a tail

• The head domain binds to an actin filament and has the ATP-hydrolyzing motor activity that enables it to move along the filament in a repetitive cycle of binding, detachment, and rebinding

myosin II

muscle cells

Rho protein family

a group of closely related monomeric GTPase proteins