Concept 11.5: Apoptosis integrates multiple cell-signaling pathways

Question 1

When signaling pathways were first discovered, they were thought to be

Answer 1

linear, independent pathways.

Question 2

For a cell to carry out the appropriate response, cellular proteins often must integrate

Answer 2

multiple signals.

Question 3

Cells that are infected, are damaged, or have reached the end of their functional life span often undergo

Answer 3

“programmed cell death”

Question 4

The best-understood type of this controlled cell suicide is

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apoptosis

Question 5

During this process, cellular agents chop up the

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DNA and fragment the organelles and other cytoplasmic components

Question 6

The cell shrinks and becomes lobed (a change called “blebbing”), and the cell’s parts are packaged up in vesicles that are

Answer 6

engulfed and digested by specialized scavenger cells, leaving no trace

Question 7

Apoptosis protects neighboring cells from damage that they would otherwise suffer if a dying cell merely leaked out all its contents, including its many

Answer 7

digestive enzymes.

Question 8

The signal that triggers apoptosis can come from either

Answer 8

outside or inside the cell.

Question 9

Outside the cell, signaling molecules released from other cells can initiate a

Answer 9

signal transduction pathway that activates the genes and proteins responsible for carrying out cell death.

Question 10

Within a cell whose DNA has been irretrievably damaged, a series of protein-protein interactions can

Answer 10

pass along a signal that similarly triggers cell death

Question 11

The molecular mechanisms of apoptosis were worked out by researchers studying embryonic development of a small soil worm, a nematode called

Answer 11

Caenorhabditis elegans

Question 12

The timely suicide of cells occurs exactly

Answer 12

131 times during normal development of C. elegans, at precisely the same points in the cell lineage of each worm.

Question 13

In worms and other species, apoptosis is triggered by signals that activate a

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cascade of “suicide” proteins in the cells destined to die.

Question 14

Genetic research on C. elegans initially revealed two key apoptosis genes, called

Answer 14

ced-3 and ced-4 (ced stands for “cell death”), which encode proteins essential for apoptosis.

Question 15

These and most other proteins involved in apoptosis are continually present in cells, but in inactive form;

Answer 15

thus, regulation in this case occurs at the level of protein activity rather than through gene activity and protein synthesis.

Question 16

In C. elegans, a protein in the outer mitochondrial membrane, called

Answer 16

Ced-9 (the product of the ced-9 gene), serves as a master regulator of apoptosis, acting as a brake in the absence of a signal promoting apoptosis

Question 17

When a death signal is received by the cell, signal transduction involves a change in

Answer 17

Ced-9 that disables the brake, and the apoptotic pathway activates proteases and DNA of the cell

Question 18

The main proteases of apoptosis are called ___________ ; in the nematode, the chief caspase is the Ced-3 protein.

Answer 18

caspases

Question 19

In humans and other mammals, several different pathways, involving about

Answer 19

15 different caspases, can carry out apoptosis.

Question 20

The pathway that is used depends on the type of

Answer 20

cell and on the particular signal that initiates apoptosis.

Question 21

One major pathway involves certain mitochondrial proteins that are triggered to form molecular pores in the mitochondrial outer membrane, causing it to

Answer 21

leak and release other proteins that promote apoptosis

Question 22

Perhaps surprisingly, these latter include

Answer 22

cytochrome c, which functions in mitochondrial electron transport in healthy cells (see Figure 9.15) but acts as a cell death factor when released from mitochondria.

Question 23

The process of mitochondrial apoptosis in mammals uses proteins similar to the nematode proteins

Answer 23

Ced-3, Ced-4, and Ced-9.

Question 24

These can be thought of as relay proteins capable of

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transducing the apoptotic signal.

Question 25

At key gateways into the apoptotic program, relay proteins integrate signals from several different sources and can send a cell

Answer 25

down an apoptotic pathway

Question 26

Often, the signal originates outside the cell, like the death-signaling molecule depicted in Figure 11.20b, which presumably was released by a

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neighboring cell.

Question 27

When a death-signaling ligand occupies a cell-surface receptor, this binding leads to activation of .

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caspases and other enzymes that carry out apoptosis, without involving the mitochondrial pathway

Question 28

In a twist on the classic scenario, two other types of alarm signals that can lead to apoptosis originate from inside the cell rather than from a

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cell-surface receptor.

Question 29

One signal comes from the

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nucleus, generated when the DNA has suffered irreparable damage,

Question 30

a second comes from the

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endoplasmic reticulum when excessive protein misfolding occurs.

Question 31

Mammalian cells make life-or-death “decisions” by somehow integrating the death signals and life signals they receive from these

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external and internal sources.

Question 32

A built-in cell suicide mechanism is essential to

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development and maintenance in all animals.

Question 33

The similarities between apoptosis genes in nematodes and those in mammals, as well as the observation that apoptosis occurs in multicellular fungi and even in single-celled yeasts, indicate that the basic mechanism evolved

Answer 33

early in the evolution of eukaryotes

Question 34

In vertebrates, apoptosis is essential for normal development of the nervous system, for normal operation of the immune system, and for normal

Answer 34

morphogenesis of hands and feet in humans and paws in other mammals

Question 35

The level of apoptosis between the developing digits is lower in the webbed feet of ducks and other water birds than in the nonwebbed

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feet of land birds, such as chickens

Question 36

In the case of humans, the failure of appropriate apoptosis can result in .

Answer 36

webbed fingers and toes

Question 37

Significant evidence points to the involvement of apoptosis in certain degenerative diseases of the nervous system, such as

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Parkinson’s disease and Alzheimer’s disease.

Question 38

In Alzheimer’s disease, an accumulation of aggregated proteins in neuronal cells activates an enzyme that triggers apoptosis, resulting in the

Answer 38

loss of brain function seen in these patients.

Question 39

Furthermore, cancer can result from a failure of

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cell suicide;

Question 40

some cases of human melanoma, for example, have been linked to

Answer 40

faulty forms of the human version of the C. elegans Ced-4 protein