Basic mechanisms in cell communication Flashcards

1
Q

Signal molecules

A

A signal molecule triggers a cellular pathway that results in a response in the target cell. The series of steps from signal molecule to response is a signaling pathway. Can be hormones released by certain controlling cells. When a target cell binds a signal molecule, it modifies its internal activities in accordance with the signal, coordinating its functions with the activities of other cells of the organism. The responses of the target cell may include changes in gene activity, protein synthesis, transport of molecules across the plasma membrane, metabolic reactions, secretion, movement, division or even “suicide”, a programmed death of the receiving cell. It can also become a controlling cell by releasing signal molecules that modify activity of other cell types.

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2
Q

Controlling cells

A

Controlling cells release many signals, but each receiving cell (target cell) has receptors that are tuned in to recognize only one or a few of the many signal molecules that circulate in its vicinity; other signal molecules pass by without effect because the cell has no receptors for them. Target cells can also become a controlling cell by releasing signal molecules that modify activity of other cell types.

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3
Q

Target cell

A

Controlling cells release many signals, but each receiving cell (target cell) has receptors that are tuned in to recognize only one or a few of the many signal molecules that circulate in its vicinity; other signal molecules pass by without effect because the cell has no receptors for them. When a target cell binds a signal molecule, it modifies its internal activities in accordance with the signal, coordinating its functions with the activities of other cells of the organism. The responses of the target cell may include changes in gene activity, protein synthesis, transport of molecules across the plasma membrane, metabolic reactions, secretion, movement, division or even “suicide”, a programmed death of the receiving cell. It can also become a controlling cell by releasing signal molecules that modify activity of other cell types.

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4
Q

Receptors

A

Controlling cells release many signals, but each receiving cell (target cell) has receptors that are tuned in to recognize only one or a few of the many signal molecules that circulate in its vicinity; other signal molecules pass by without effect because the cell has no receptors for them.

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5
Q

Signaling pathway

A

A signal molecule triggers a cellular pathway that results in a response in the target cell. The series of steps from signal molecule to response is a signaling pathway. The total network of signaling pathways allows multicellular organisms to grow, develop, reproduce and compensate for environmental changes in an internally coordinated fashion.

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6
Q

Homeostasis

A

The total network of signaling pathways allows multicellular organisms to grow, develop, reproduce and compensate for environmental changes in an internally coordinated fashion. Maintaining the internal environment within a narrow tolerable range is homeostasis.

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7
Q

Cell signaling

A

The system of communication between cells through signaling pathways is called cell signaling. Research in cell signaling is a highly important field of biology, motivated by the desire to understand the growth, development and function of organisms.

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8
Q

Direct contact

A

Cells communicate with one another in three ways. 1 The first is called direct contact, it is when adjacent cells have direct channels linking their cytoplasm’s. In this rapid means of communication, small molecules and ions exchange directly between the 2 cytoplasm’s. In animal cells, the direct channels of communication are gap junctions, the specialized connections between the cytoplasm’s of adjacent cells. In plant cells, the direct channels of communication are plasmodesmata. Small molecules moving between adjacent cells in plants include certain plant hormones that regulate growth. In this way, plant hormones are distributed to other cells. Cells can also communicate directly through cell-cell recognition.

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9
Q

Gap junctions

A

In animal cells, the direct channels of communication are gap junctions, the specialized connections between the cytoplasm’s of adjacent cells. The main role of gap junctions is to synchronize metabolic activities or electrical signals between cells in a tissue. For example, gap junctions play a key role in spreading electrical signals from one cell to the next in cardiac muscle.

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10
Q

Cell-cell recognition

A

Cells can also communicate directly through cell-cell recognition. In this process, animal cells with particular membrane-bound cell-surface molecules dock with one another, initiating communication between the cells. For example, cell-cell recognition of this kind activates particular cells in a mammals immune system in order to mount an immune response.

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11
Q

Local signaling

A

Cells communicate with one another in three ways. 2 The second way is by local signaling. In local signaling, a cell releases a signal molecule that diffuses through the extracellular fluid (the aqueous fluid surrounding and between the cells) and causes a response in nearby target cells. Here, the effect of cell signaling is local, so the signal molecule is called a local regulator and the process is called paracrine regulation.

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12
Q

Extracellular fluid

A

In local signaling, a cell releases a signal molecule that diffuses through the extracellular fluid (the aqueous fluid surrounding and between the cells) and causes a response in nearby target cells.

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13
Q

Local regulator

A

Here in the extracellular fluid, the effect of cell signaling is local, so the signal molecule is called a local regulator and the process is called paracrine regulation. In some cases the local regulator acts on the same cell that produces it, and this is called autocrine regulation.

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14
Q

Paracrine regulation

A

Cells communicate with one another in three ways. 2 The second way is by local signaling. In local signaling, a cell releases a signal molecule that diffuses through the extracellular fluid (the aqueous fluid surrounding and between the cells) and causes a response in nearby target cells. Here, the effect of cell signaling is local, so the signal molecule is called a local regulator and the process is called paracrine regulation. In some cases the local regulator acts on the same cell that produces it, and this is called autocrine regulation. For example, many of the growth factors that regulate cell division are local regulators that act in both a paracrine and autocrine fashion.

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15
Q

Autocrine regulation

A

Here in the extracellular fluid, the effect of cell signaling is local, so the signal molecule is called a local regulator and the process is called paracrine regulation. In some cases the local regulator acts on the same cell that produces it, and this is called autocrine regulation. For example, many of the growth factors that regulate cell division are local regulators that act in both a paracrine and autocrine fashion.

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16
Q

Long-distance signaling

A

Cells communicate with one another in three ways. 3 The third is long distance signaling. In this form of communication, a controlling cell secretes a long distance signaling molecule called a hormone. This method is the most common means of cell communication. Hormones are found in both animals and plants. In animals, hormones secreted by controlling cells enter the circulatory system where they travel to target cells elsewhere in the body. For example, in response to stress, cells of mammal’s adrenal glands (located on top of the kidneys) -the controlling cells, secrete the hormone epinephrine (also known as adrenaline) into the bloodstream. In short, a controlling cell releases a signal molecule that causes a response (affects a function) in target cells. Target cells process the signal in 3 sequential steps.

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17
Q

Hormone

A

In this form of communication, long distance signaling, a controlling cell secretes a long distance signaling molecule called a hormone. This method is the most common means of cell communication. Hormones are found in both animals and plants. In animals, hormones secreted by controlling cells enter the circulatory system where they travel to target cells elsewhere in the body. For example, in response to stress, cells of mammal’s adrenal glands (located on top of the kidneys) -the controlling cells, secrete the hormone epinephrine (also known as adrenaline) into the bloodstream. In plants, most hormones travel to target cells by moving through cells rather than by moving through vessels. Some plant hormones are gases that diffuse through the air to the target tissues.

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18
Q

Epinephrine

A

For example, in response to stress, cells of mammal’s adrenal glands (located on top of the kidneys) -the controlling cells, secrete the hormone epinephrine (also known as adrenaline) into the bloodstream. Epinephrine acts on target cells to increase the amount of glucose in the blood.

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19
Q

Glycogen phosphorylase

A

The hormone epinephrine activates the enzyme glycogen phosphorylase. In the liver, this enzyme catalyzes the breakdown of glycogen, a polymer of glucose molecules, into glucose molecules, which are then released into the bloodstream. The overall effect of this response to epinephrine secretion is to supply energy to the major muscles responsible for locomotion, the body is now ready for physical activity or to handle stress.

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20
Q

Reception

A

In short, a controlling cell releases a signal molecule that causes a response (affects a function) in target cells. Target cells process the signal in 3 sequential steps. 1 The first part of processing the signal is reception, it is the binding of a signal molecule with a specific receptor of target cells. Target cells have receptors that are specific for the signal molecule, which distinguishes them from cells that do not respond to the signal molecule. The signals themselves may be polar (charged, hydrophilic) molecules or nonpolar (hydrophobic) molecules, and their receptors are shaped to recognize and bind them specifically. Receptors for polar signal molecules are embedded in the plasma membrane with a binding site for the signal molecule on the cell surface. Receptors for nonpolar molecules are located within the cell. Steroids such as testosterone and estrogen are examples of nonpolar signal molecules.

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21
Q

Transduction

A

In short, a controlling cell releases a signal molecule that causes a response (affects a function) in target cells. Target cells process the signal in 3 sequential steps. 2 The second step in the process is transduction. It is the process of changing the signal into the form necessary to cause the cellular response. The initial signal binds to and activates the receptor, changing it to a form that initiates transduction. Transduction typically involves a cascade of reactions that include several different molecules, referred to as a signaling cascade.

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22
Q

Signaling cascade

A

The initial signal binds to and activates the receptor, changing it to a form that initiates transduction. Transduction typically involves a cascade of reactions that include several different molecules, referred to as a signaling cascade. For example, after epinephrine binds to its surface receptor, the signal is transmitted through the plasma membrane into the cell to another protein, which in turn, causes the production of numerous small second messenger molecules. As we shall see later, both protein and second messengers can be part of the signaling cascade that results in triggering a cellular response.

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23
Q

Response

A

In short, a controlling cell releases a signal molecule that causes a response (affects a function) in target cells. Target cells process the signal in 3 sequential steps. 3 The third part of the process is the response. Last, the transduced signal causes a specific cellular response. That response depends on the signal and the receptors of the target cell. In epinephrine, the response was activation of the enzyme glycogen phosphorylase. The active enzyme catalyzes the conversion of stored glycogen to glucose, which is the response to the signal delivered by epinephrine.

24
Q

Quorum sensing

A

In the process of quorum sensing, bacteria release signal molecules in increasing concentration as cell density increases. The molecules are sensed by the cells in the population, and each cell then responds to adapt to the changing environment.

25
Q

Polar signal molecules

A

Cell communication systems using surface receptors have 3 components. 1, the extracellular signal molecules released by the controlling cells. 2, The surface receptors on target cells that receive the signals and 3, The internal response pathways triggered when receptors bind a signal. Surface receptors in mammals and other vertebrates recognize and bind polar, water-soluble signal molecules. These molecules are released by controlling cells and enter the extracellular fluid, and then pass into the blood circulation (in animals with a circulatory system). Two major types of polar signal molecules are polar hormones (hormones that are not steroids) and neurotransmitters. Examples of polar hormones are epinephrine and peptide hormones, which, as a group, affect all body systems, like insulin regulating sugar levels in the blood. Neurotransmitters are molecules released by neurons that trigger activity in other neurons or other cells in the body; they include small peptides, individual amino acids or their derivatives, and other chemical substances.

26
Q

Surface receptors

A

The surface receptors that recognize and bind signal molecules are all glycoproteins, proteins with attached carbohydrates chains. They are integral proteins that extend entirely through the plasma membrane. Typically the signal-binding site of the receptor is part of the protein that extends from the outer membrane surface, and which is folded in a way that closely fits the signal molecule. The fit is specific, so a particular receptor binds only one type of signal molecule or a closely related group of signal molecules. A signal molecule brings about specific changes in cells to which it binds. When a signal molecule binds to a surface receptor, the molecular structure of that receptor changes so that it transmits the signal through the plasma membrane, activating the cytoplasmic end of the receptor. The activated receptor then initiates the first step in a cascade of molecular events, the signaling cascade that triggers the cellular response. Animals typically have 100s to 1000s of surface receptors representing a variety of types. Receptors for a specific peptide hormone may number between 500 to 100.000 or more per cell. Different cell types have different receptors. The combination of surface receptors on one cell type varies overtime. Changes also occur as normal cells are transformed into cancer cells.

27
Q

Protein kinases

A

Signal transduction pathways have 3 characteristics, 1 Binding of a signal molecule to a surface receptor is sufficient to trigger the cellular response, the signal molecule does not enter the cell. Many drugs are mimics of the hormones that activate receptors, so that they bind to the receptors or proteins, keeping them from being activated or doing their function, like beta-blockers or PCSK9 inhibitors that sit on the protein that breaks down receptors on the liver that reduces LDL (cholesterol). 2 The signal is relayed inside the cell by protein kinases, enzymes that transfer a phosphate group from ATP to one or more sites on particular proteins.

28
Q

Phosphorylation cascade

A

2nd characteristic of signal transduction pathways. The signal is relayed inside the cell by protein kinases, enzymes that transfer a phosphate group from ATP to one or more sites on particular proteins. Protein kinases often act in a chain catalyzing a series of phosphorylation reactions called a phosphorylation cascade, the pass a signal along. The first kinase catalyzes phosphorylation of the second, which then becomes active and phosphorylates the third kinase which becomes active and so on. The last protein in the cascade is the target protein.

29
Q

Target protein

A

2nd characteristic of signal transduction pathways. The last protein in the phosphorylation cascade is the target protein. Phosphorylation of a target protein stimulates or inhibits its activity depending on the particular protein. This change in activity brings about the cellular response. For example, phosphorylating a target protein that regulates whether a set of genes are turned on or off could cause the cells to start or stop producing the proteins the genes encode. The change in this set of proteins causes a response related to the functions of those proteins.

30
Q

Protein phosphatases

A

2nd characteristic of signal transduction pathways. The effects of protein kinases are balanced or reversed by another group of enzymes called protein phosphatases, which remove the phosphate groups from target proteins. Unlike protein kinases that have to be activated by a signal molecule binding to a surface receptor, most of the protein phosphatases are continually active in cells. That way they are continually removing phosphate groups from target proteins, and quickly shuts off a signal transduction pathway if its signal molecule is no longer bound at the cell surface.

31
Q

Amplification

A

3rd characteristic of signal transduction pathways. An increase in the magnitude of each step occurs as a signal transduction pathway proceeds, a phenomenon called amplification. Amplification occurs because many of the proteins that carry out individual steps in the pathway, including protein kinases, are enzymes. Once activated, each enzyme can activate hundreds of proteins including other enzymes that enter the next step in the pathway. Generally, the more enzyme-catalyzed steps in a response pathway, the greater the amplification. As a result, just a few extracellular signal molecules binding to their receptors can produce a full internal response. For similar reasons, amplifications also occur for signal transduction pathways that involve internal receptors.

32
Q

Off switches

A

Importantly, all signaling pathways have off switches that serve to stop the cellular response when no such response is needed. In signaling transduction pathways, that is protein phosphatases for a phosphorylation cascade. Once signal molecules are released into the body’s circulation, they remain for only a certain time. Either they are broken down at a steady rate by enzymes in organs such as the liver or they are excreted in the kidneys. The removal process ensures that they are only active for as long as controlling cells are secreting them. As signal transduction runs its course, the receptors and their bound signal molecules are removed from the target cell surface by endocytosis. Both the receptor and its bound signal molecule may be degraded in lysosomes after entering the cell or the receptors may be separated from the signal molecules and recycled to the cell surface.

33
Q

Receptor tyrosine kinases

A

One major type of surface receptors, the receptor tyrosine kinases, have their own protein kinase activity on the cytoplasmic end of the protein. Binding of a signal molecule to this type of receptor turns on the receptors built in protein kinase, which leads to activation of the receptor. The activated receptor then initiates a signaling cascade, which results in cellular response. For this type of receptor, initiation of transduction occurs when two receptor molecules each bind a signal molecule in the reception step, move together in the membrane, and assemble into a dimer (a pair of monomers bonded together). The protein kinases of each receptor monomer are activated by dimer formation, and they phosphorylate the partner monomer in the dimer, a process called autophosphorylation. Receptor tyrosine kinases are found in all multicellular animals, but not plants or fungi. 58 genes in humans code for receptor tyrosine kinases. They are important, and have functions such as binding hormones like insulin.

34
Q

Autophosphorylation

A

The protein kinases of each receptor monomer are activated by dimer formation, and they phosphorylate the partner monomer in the dimer, a process called autophosphorylation. The phosphorylation is of tyrosine amino acids, which gives this type of receptors their name. The multiple phosphorylations activate many different sites on the dimer. When a signaling protein binds to an activated site, it initiates a transduction pathway leading to a cellular response. Since different receptor tyrosine kinases bind different combinations of signaling proteins, the receptors initiate different responses.

35
Q

Insulin

A

Receptor tyrosine kinases are important, because they are responsible for binding the peptide hormone insulin, a regulator of carbohydrate metabolism, trigger diverse cellular responses, including effects on glucose uptake, the rates of many metabolic reactions, and cell growth and division. The insulin receptor is exceptional because it is permanently in a tetrameric form.

36
Q

Epidermal growth factor

A

Something receptor tyrosine kinases bind for.

37
Q

Platelet-derived growth factor

A

Something receptor tyrosine kinases bind for.

38
Q

Nerve growth factor

A

Something receptor tyrosine kinases bind for.

39
Q

Diabetes

A

Some hereditary defects in the insulin receptor are responsible for some forms of diabetes, a disease in which glucose accumulates in the blood, because it cannot be absorbed in sufficient quantity by body cells.

40
Q

G protein-coupled receptors

A

Another large family of surface receptors, is known as the G protein-coupled receptors, they respond to a signal by activating an inner membrane protein called a G protein, which is closely associated with the cytoplasmic end of the receptor. G proteins are named so, because they bind the guanine nucleotides GDP and GTP. These receptors are found in animals, plants, fungi and certain protists. Almost all of the receptors in this group are large glycoproteins built up from a single polypeptide chain anchored in the plasma membrane by 7 segments of the amino acid chain that zigzag back and forth across the membrane 7 times. Unlike receptor tyrosine kinases, G protein coupled receptors lack a built in protein kinase activity. They are responsible for things like smell, sight, hormones and neurotransmitters.

41
Q

GDP

A

Guanosine diphosphate.

42
Q

GTP

A

Guanosine triphosphate.

43
Q

First messenger

A

In signal transduction pathways controlled by G protein coupled receptors, the extracellular signal molecule is called the first messenger. The binding of the first messenger to the receptor activates it. Coupled to the receptor is a G protein, which is called a molecular switch because it switches between an inactive form with GDP bound to it and an active form where it has GTP bound in the same place. When the first messenger activates the receptor, it activates the G protein by causing it to release GDP and bind GTP. If the first messenger is released or the receptor is taken in by endocytosis, GTP is hydrolyzed to GDP, which inactivates it. That turns the effector off.

44
Q

Effector

A

The GTP bound subunit of the G protein breaks off and binds to a plasma membrane-associated enzyme called the effector, activating it. The activated effector now generates one or more internal, nonprotein signal molecules called second messengers. As long as a G protein-coupled receptor is bound to a first messenger, the receptor keeps the G protein active, which keeps the effector active in generating second messengers.

45
Q

Second messenger

A

The activated effector now generates one or more internal, nonprotein signal molecules called second messengers. The second messengers directly or indirectly activate protein kinases, which elicit the cellular response by adding phosphate groups to specific target proteins. The separate protein kinases of these pathways all add phosphate groups to serine or threonine amino acids in their target proteins, which typically are,
- Enzymes that catalyze steps in metabolic pathways.
- Ion channels in the plasma and other membranes.
Regulatory proteins that control gene activity and cell division.

46
Q

Cyclic AMP (cAMP)

A

Two major G protein coupled receptor response pathways involve different second messengers. Activated G proteins bring about a cellular response through two major receptor-response pathways in which different effectors generate different second messengers. One pathway involves the second messenger cyclic AMP (cAMP cyclic 3’,5’-adenosine monophosphate), a relatively small, water soluble molecule derived from ATP. The effector that produces cAMP is the enzyme adenylyl cyclase, which converts ATP to cAMP. cAMP diffuses through the cytoplasm and activates protein kinases that add phosphate groups to target proteins. The off switch quickly converts cAMP to AMP by phosphodiesterase. Or endocytosis.

47
Q

Inositol triphosphate (IP3)

A

Two major G protein coupled receptor response pathways involve different second messengers. Activated G proteins bring about a cellular response through two major receptor-response pathways in which different effectors generate different second messengers. The other pathway involves two second messengers: inositol triphosphate (IP3) and diacylglycerol (DAG). IP3 is a small water soluble molecule that diffuses rapidly through the cytoplasm. The primary effect of IP3 in animal cells is to activate transport proteins in the ER which release Ca2+ stored in the ER into the cytoplasm. It alone, or in combination with DAG, activates a protein kinase cascade that brings about the cellular effect.

48
Q

Diacylglycerol (DAG)

A

Two major G protein coupled receptor response pathways involve different second messengers. Activated G proteins bring about a cellular response through two major receptor-response pathways in which different effectors generate different second messengers. The other pathway involves two second messengers: inositol triphosphate (IP3) and diacylglycerol (DAG). DAG is hydrophobic; it remains and functions in the plasma membrane.

49
Q

Phospholipase C

A

The effector of the second pathway, is an enzyme called phospholipase C, that produces both IP3 and DAG by breaking down a membrane phospholipid.

50
Q

Phosphodiesterase

A

The off switch quickly converts cAMP to AMP by phosphodiesterase. Or endocytosis.

51
Q

Fura-2/Quin-2

A

Used as indicators that Ca2+ ions are released. They are water soluble. They emit light when exposed to ultraviolet light, and the wavelength of the fluorescence differs depending on whether the molecules are bound to or free of Ca2+, therefore the amount of Ca2+ can be quantified by measuring the amount of fluorescence at each of the two wavelengths.

52
Q

Bipolar disorder

A

IP3/DAG pathways have been linked to mental disorders, particularly bipolar disorder, in which patients experience periodic changes in mood. Lithium has been used for many years as a therapeutic agent for bipolar disorder. Recent research has shown that lithium reduces the activity of IP3/DAG pathways that release neurotransmitters; among them are some neurotransmitters that take part in brain function. Lithium also relieves cluster headaches and premenstrual tension, suggesting that they may be linked to these conditions as well.

53
Q

Cytokinins

A

In plants, IP3/DAG pathways control responses to conditions such as water loss and changes in light intensity or salinity. Plant hormones, relatively small, nonprotein molecules such as the cytokinins (derivatives of the nucleotides base adenine), act as first messengers activating some of the IP3/DAG pathways of these organisms.

54
Q

Mitogen-activated protein kinases (MAP kinases)

A

Some pathways important in gene regulation link certain receptor tyrosine kinases to a specific type of G protein called Ras. When the receptor tyrosine kinase receives a signal (step 1), it activates by autophosphorylation (step 2). Adapter proteins then bind to the phosphorylated receptor and bridge to Ras, causing GTP to bind to, and activate Ras (step 3). The activated Ras sets in motion a phosphorylation cascade that involves a series of 3 enzymes known as mitogen-activated protein kinases (MAP kinases, step 4). The last MAP kinase in the cascade, when activated, enters the nucleus (step 5), and phosphorylates other proteins, which then change the expression of certain genes, particularly activating those involved in cell division (step 6). A mitogen is a substance that controls cell division, hence the name of the kinases.

55
Q

Steroid hormone receptors

A

Cells of many types have internal receptors that respond to signals arriving from the cell exterior. Unlike signal molecules that bind to surface receptors, these signals, primarily steroid hormones, penetrate through the plasma membrane to trigger response pathways inside the cells. The internal receptors, called steroid hormone receptors, are typically control proteins that turn on (sometimes off) specific genes when they are activated by binding a signal molecule. They are relatively small, nonpolar molecules derived from cholesterol, with chemical structure based on 4 carbon rings. Steroid hormones combine with hydrophilic carrier proteins that mask their hydrophobic groups and hold them in solution in the blood and extracellular fluids. When a steroid hormone-carrier protein complex contacts the surface of the cell, the hormone is released and penetrates directly through the plasma membrane. On the cytoplasmic side, the hormone binds to its internal receptor.

56
Q

Cross-talk

A

Cells are under the continual influence of many simultaneous signal molecules. The cell signaling pathways may operate independently, or communicate with one another to integrate their responses to cellular signals coming from different controlling cells. The interpathway interaction is called cross-talk; a conceptual example that involves two second messenger pathways. For example, a protein kinase in one pathway might phosphorylate a site on a target protein in another signal transduction pathway, activating or inhibiting that protein, depending on the site of phosphorylation. The cross-talk can be extensive, resulting in a complex network of interactions between cell communication pathways. Cross-talk often leads to modifications of the cellular responses controlled by the pathways. It fine tunes the effects of combinations of signal molecules binding to the receptors of a cell. Direct channels of communication may also be involved in a cross-talk network. For example, gap junctions between the cytoplasms of adjacent cells admit ions and small molecules, including the Ca2+, cAMP and IP3 second messengers released by the receptor-response pathways. One cell that receives the signal can therefore coordinate their function with other cells in the same tissue. This takes place in cardiac muscle tissue.