WEEK 4 (Intercellular communication and signal transduction)

Question 1

What is intercellular communication divided into?

Answer 1

• Direct (Gap junctions, TNTs, linkup of surface markers)
• Indirect (extracellular chemical messengers)

Question 2

What are the extracellular chemical messengers?

Answer 2

• Paracrines/Autocrines
• Neurotransmitters
• Hormones
• Neurohormones

Question 3

What is the function of gap junctions?

Answer 3

They allow the free movement of ions between neurons

Question 4

What is the difference between paracrine and autocrine signalling?

Answer 4

In paracrine signalling a cell targets a neighbouring cell and in autocrine signalling a cel targets itself

Question 5

Where are neuromuscular junctions found?

Answer 5

Between presynaptic neurons and target muscles

Question 6

What is signal transduction?

Answer 6

The process in which binding of an extracellular messenger to the cell receptor is translated into changes in biochemistry, cell biology and gene transcription that make it possible for the cell to respond to the information that was received

simpler definition: The process in which the extracellular signal is transduced or changed into a form necessary to modify intracellular activities to accomplish the desired outcome

Question 7

What is the importance of the difference between lipid soluble neurotransmitters and lipid insoluble neurotransmitters?

Answer 7

Lipid insoluble neurotransmitters act on the receptors on the surface of the cell surface membrane whereas the lipid soluble neurotransmitters enter the postsynaptic cell and act on the receptors within

Question 8

Which gated channels can be found on the cell surface membrane of the postsynaptic neuron?

Answer 8

Chemically gated channels/Ligand gated channels

Question 9

What happens in gap junctions?

Answer 9

Ions and small molecules are directly exchanged between closely associated interacting cells without ever entering the extracellular fluid

Question 10

What is the function of tunnelling nanotubes (TNTs)?

Answer 10

Intercellular bridges that serve as a route for selective, relatively long transfer from one cell to another of large cargo (e.g proteins and organelles)

Question 11

What is the major difference between TNTs and gap junctions?

Answer 11

TNTs can transfer larger cargo considerably longer distances than gap junctions can

Question 12

What is the mechanism behind the transient direct link up of surface markers?

Answer 12

Cells with specialised markers on the surface membrane allow them to directly link with certain cells that have compatible markers for transient interactions

(this is how cell-destroying immune cells specifically recognise and selectively destroy only undesirable cells)

Question 13

What are the four types of extracellular chemical messengers or “signal molecules”?

Answer 13

Paracrines/autocrines
Neurotransmitters
Hormones
Neurohormones

Question 14

To exert its effect, an extracellular chemical messenger must bind with the target cell receptors ____________ for it

Answer 14

Specific

Question 15

What percentage of all genes in humans code for synthesis of these membrane receptors?

Answer 15

5%

Question 16

The four types of extracellular chemical messengers differ in their ______________ and the _____________ to and means by which they get to their site of action

Answer 16

Source
Distance

Question 17

Why are Paracrines restricted to short distances and why do they not gain entry to the blood?

Answer 17

Paracrines are distributed by simple diffusion within the interstitial fluid so their action is restricted to short distances

They do not gain entry to the blood in any significant quantity because they are rapidly inactivated by locally existing enzymes

Question 18

What is an example of a Paracrine and what is its function?

Answer 18

Histamine

Released from a specific type of connective tissue cell during an inflammatory response within an invaded or injured tissue. Histamine dilates the blood vessels which increases blood flow to the tissue and brings additional blood-borne combat supplies into the affected area

Question 19

Define “Hormones”

Answer 19

Long-range chemical messengers specifically secreted into the blood by endocrine glands in response to an appropriate signal

Question 20

How are non-target cells not influenced by any blood-borne hormones that reach them?

Answer 20

Only target cells of a particular hormone have membrane receptors for binding with this hormone

Question 21

What are neurohormones?

Answer 21

Hormones released into the blood by neurosecretory neurons

Question 22

What is the difference between a neuron and a neurosecretory neuron?

Answer 22

Neurons directly innervate target cells and release a neurotransmitter into the synaptic cleft whereas neurosecretory neurons release neurohormones into the blood to distant target cells

Question 23

What are the two types of signal transduction?

Answer 23

1. Lipid-soluble extracellular chemical messengers
2. Water-soluble extracellular chemical messengers

Question 24

Describe the function of lipid-soluble extracellular chemical messengers

Answer 24

These chemical messengers dissolve in and pass through the lipid bilayer of the target cell’s plasma membrane and bind to receptors inside the target cell to initiate the desired intracellular response such as controlling the level of activity of the transcribed protein

Question 25

What happens when lipid soluble extracellular chemical messengers bind to their receptors?

Answer 25

Binding causes change in gene activity either by turning on or suppressing transcription of specific genes

Question 26

Describe the function of water-soluble extracellular chemical messengers

Answer 26

These chemical messengers bind to specific receptors on the outer surface of the plasma membrane which triggers a sequence of intracellular events that controls a particular cellular activity

Question 27

What is the pathway used by lipid-soluble extracellular messengers that bind to intracellular receptors?

Answer 27

Function in nucleus to change specific gene activity

Question 28

What are the pathways used by water-soluble extracellular messengers that bind to surface membrane receptors?

Answer 28

- Bind to open and close chemically gated receptor-channels - Bind to and activate receptor-enzyme complexes (Use TYROSINE KINASE PATHWAY where the receptor itself functions as an enzyme or use JAK/SAT PATHWAY where the receptor and attached enzymes function as a unit) - Bind to G-protein-coupled receptors (GPCRs) and activate second-messenger pathways

Question 29

What are the three general responses of a water-soluble extracellular messenger binding to its receptor?

Answer 29

- binding to a chemically gated receptor-channel opens or closes the channel with the resultant ion movement leading to the cell’s response - binding to a receptor-enzyme complex activates tyrosine kinase which phosphorylates designated proteins that lead to a cell’s response - binding to a G-protein-coupled receptor activates a second-messenger pathway that carries out the cell’s response

Question 30

What are ‘protein kinases’?

Answer 30

The name for any enzyme that transfers a phosphate group from ATP to a particular intracellular protein

Question 31

Since phosphorylation of a single protein does not get the job done, protein kinases act in a chain of reactions called a ____________ to pass along the signal to the final designated proteins capable of carrying out the desired effect

Answer 31

Cascade

Question 32

Describe the stages of the Tyrosine Kinase pathway

Answer 32

1. Two extracellular messengers bind to two tyrosine kinase receptor-enzymes, which pair, activating receptor-enzyme’s protein kinase (tyrosine kinase) site that faces the cytoplasm 2. Tyrosine kinase site self-phosphorylates receptor-enzyme’s tyrosines 3. Inactive designated protein binds to phosphorylated receptor-enzyme, which phosphorylates protein, activating it 4. Active designated protein brings about desired response

Question 33

In the JAK/STAT pathway where does the tyrosine kinase activity take place?

Answer 33

In separate cytosolic enzymes called Janus family tyrosine kinases (JAKs)

Question 34

Describe the JAK/STAT pathway

Answer 34

1. The receptor and attached enzymes function as a unit and two JAKs are attached (one on each side) to the receptor in the cytoplasm 2. Binding of an extracellular messenger to the receptor on the ECF side causes a conformational change in the receptor that activates the JAKs bound to the cytosolic side of the receptor 3. Activated JAKs phosphorylate signal transducers and activators of transcription (STAT) within the cytosol 4. Phosphorylated STAT moves to the nucleus and turns on transcription of selected genes resulting in the synthesis of new proteins that carry out the cellular response

Question 35

What is an example of a hormone that uses the JAK/STAT pathway?

Answer 35

Prolactin stimulates milk secretion in lactating mothers

Question 36

Describe the G-protein-coupled receptor (GPCR) pathway

Answer 36

1. Extracellular (first) messenger binds to the G-protein-coupled receptor which activates the G protein 2. The G protein shuttles along the membrane to activate the effector protein 3. Effector produces a second messenger 4. Second messenger activates protein kinase; the protein kinase then activates a designated protein 5. Active designated protein brings about desired cellular response

Question 37

What is distinguishable about the G-protein-coupled receptor (GPCR)?

Answer 37

It snakes through the membrane and is attached to a G protein

Question 38

How can extracellular messengers be removed when no longer needed?

Answer 38

- degraded by the liver and and excreted in urine - removed by receptor-mediated endocytosis (both the receptor and extracellular messenger are internalised by the target cell)

Question 39

What is the name of a group of enzymes that reverse the effects of JAK/STAT and second-messenger signal transduction pathways?

Answer 39

Protein-phosphatases They remove phosphate groups from designated proteins. The continual removal of phosphate groups from designated proteins quickly shut off a signal transduction pathway if a signal molecule is no longer bound at the cell surface

Question 40

What is the difference between kinases and phosphatases?

Answer 40

Kinases activate a signaling pathway by phosphorylating designated proteins whereas phosphatases inactivate the pathway by dephosphorylating these proteins

Question 41

Paracrines are either _____________ or _______________

Answer 41

Cytokines Eicosanoids

Question 42

What are Cytokines?

Answer 42

A collection of protein signal molecules secreted by cells of the immune system and other cell types that largely act locally to regulate immune responses

Question 43

What are Eicosanoids?

Answer 43

A group of lipid signal molecules derived from a fatty acid in the plasma membrane of most cell types that act locally to regulate diverse cellular processes throughout the body

Question 44

What are the different functions of Cytokines?

Answer 44

- regulates numerous activities of the immune system (e.g mediating inflammation, enhancing the activity of antibody-producing cells and virus-fighting cells) - influencing cell growth and cell differentiation

Question 45

What are Cytosines important in development referred to specifically as?

Answer 45

Growth factors

Question 46

Which pathways do Cytokines usually function in?

Answer 46

Immune cytokines employ the JAK/STAT pathways and growth factors use the tyrosine kinase pathway

Question 47

What happens to Eicosanoids once they act?

Answer 47

- Rapidly inactivated by local enzymes before they gain access to the blood - if circulatory system is reached, they are swiftly degraded through the lungs

Question 48

What are Eicosanoids and how are they formed into their classes?

Answer 48

Eicosanoids are a group of lipid signal molecules that act locally as paracrines to regulate physiological processes. They are modified 20-carbon fatty acids derived from arachidonic acid (a 20-carbon polyunsaturated fatty acid). Arachidonic acid is split from the plasma membrane by a membrane-bound enzyme “Phospholipase A” which is converted into either PROSTAGLANDINS, THROMBOXANES and LEUKOTRIENES depending on the enzyme. Cyclooxygenase (COX) = Prostaglandins & Thromboxanes Lipopxygenase (LOX) = Leukotrienes