W5 Cell communication&signalling/Lec8

Question 1

What are gap/communicating junctions? (description of features)
What do gap junctions allow the exchange of?

Answer 1

-They consist of 2 cylindrical channels (connexons composed of 6 connexin proteins each) on the plasma membrane of adjacent cells that are joined together to form a pore.

• Allowing direct and bidirectional exchange of
  molecules/ions between 2 neighbour cells
• No effect in cell-ECM adhesions

Question 2

What are the 3 types of junctions?

Answer 2

Gap junctions, anchoring junctions and tight junctions.

Question 3

What are the 5 types of cell signalling?

Answer 3

Contact-dependent
Paracrine
Synaptic
Endocrine
Autocrine

Question 4

What is contact-dependent signalling?
What does a signal molecule bind to?
How are the signals exchanged?

Answer 4

=Signals between interacting cells

• A signal molecule binds to a receptor on an interacting cell
  Interactions between immune cells (to induce an immune response against specific microorganisms)
• Signals exchange via gap junctions

Question 5

What is the cell-signalling pathway?

Answer 5

Divided into 3 steps
1. Signal-receptor binding
2. Signal transduction
3. Specific cell response

Question 6

Where are intracellular receptors found?

Answer 6

In the cytosol or nucleus of target cells.

Question 7

What are the 3 main classes of cell-membrane receptors?

Answer 7

1. Ion channel-coupled receptors
2. G protein-coupled receptors (GPCRs)
   3.Enzyme-coupled receptors

Also Cytosolic and nuclear receptors

Question 8

What are Ion channel-coupled receptors?
What is an example?
Where are they found

Answer 8

• The receptor conformational change after binding to the signal activates an ion channel acting as a gate for specific ions, changing the intracellular charge
• Converting chemical signals into electrical ones (nerve impulse conduction)
• Nicotinic Acetylcholine Receptor
• Nerve cells and other electrically excitable cells such as muscle cells

Question 9

What are G proteins-coupled receptors (GPCRs)?

Answer 9

• Largest class of cell-surface receptors
• G proteins-linked receptors have a common structure, with 2 components

Question 10

What type of cell signalling occurs over long distances?

Answer 10

Endocrine system

Question 11

Cell communication in which neurons release neurotransmitters to excite or inhibit the activity of other neurons or target cells?

Answer 11

Synaptic

Question 12

What is the Cell communication between distant cells, in which the signal molecules are hormones.

(Hormones are produced by endocrine cells and travel through the blood to reach distant parts of the body)

Answer 12

Endocrine

Question 13

What is the Cell communication with their immediate neighbour cells through a direct membrane–membrane contact?

Answer 13

Contact-dependent signalling

Question 14

What is the Cell signalling mediated by molecules, which act on the same cells that produce them?

Answer 14

Autocrine

Question 14

Cell signalling mediated by molecules, which act on the same cells that produce them

Answer 14

Autocrine

Question 15

What is the Cell communication in which a cell produces signal molecules, which are released into the extracellular space and act on nearby cells?

Answer 15

Paracrine

Question 16

What are the sequence of events that occur in cell signalling? (4)

Answer 16

1. Production and secretion of signal molecules
2. Signal recognition by a specific receptor
3. Receptor rearrangement to transduce the extracellular signal into intracellular signal(s) along a signal-transduction pathway
4. Trigger of a specific cellular response (activation/regulation)

Question 17

Which statement about GCPRs is not correct?
A. The receptor of GPCRs comprises 7 transmembrane helices
B. The G protein acts as an on/off switch. When associated with GDP, G protein is inactive
C. Activation of trimeric G proteins release both the α subunit and a βγ complex, which can interact and activate ion channels or enzymes
D. G proteins can act as ATPase enzymes to hydrolyze ATP to ADP
E. Once it binds to the specific extracellular signal, GPCR undergoes a conformational change that activates a G protein on the cytosolic face

Answer 17

D is not correct

Question 18

GDP and GTP (For info)

Answer 18

Trimeric G proteins are composed of three protein subunits—α, β, and γ. The α subunit is associated with GDP or GTP (not ATP/ADP). In the unstimulated state, the α subunit interacts with β,γ complex and has GDP bound to it. Binding of a specific extracellular signal molecule leads the receptor to change conformation, which in turn alters the conformation of the bound G protein and the α subunit exchanges its GDP for GTP. This exchange activates both the α subunit and a βγ complex, which dissociate to interact with their preferred target proteins (protein channels or enzymes) until the signal molecule is bound to the receptor. The whole system can be shut down quickly when the extracellular signal molecule is no longer present as the α subunit has an intrinsic GTPase activity and it hydrolyses GTP to GDP, returning to the original and inactive conformation.

Question 19

Which of the following are examples of second messenger molecules?
Cyclic AMP (cAMP)
Hormones
GTP
Ca2+
Receptor Tyrosine Kinases (RTKs)

Answer 19

Cyclic AMP and Ca2+ are correct.

Question 20

What are second messengers?

Answer 20

They are intracellular signalling molecules that are released upon the activation of a specific enzyme or protein channel following the interaction between an extracellular signalling molecule and a specific receptor.

Once activated, the enzymes/channels generate/release large quantities of second messengers, which rapidly diffuse within the cell, thereby amplifying the intracellular signal and triggering the intracellular signal transduction cascades.

Question 21

Examples of intracellular signalling molecules?

Answer 21

Cyclic AMP, Ca2+, cyclic GMP, inositol triphosphate or IP3, diacylglycerol or DAG

Question 22

Which of the following options about cell signalling is correct?

A. All kinds of receptors are located in the plasma membrane
B. One specific signal molecule or first messenger can induce only one cell response in different target cells
C. Second messengers are trans-membrane receptors
D. Ligand-Receptor recognition is not specific
E. The activity of proteins can be regulated or switched on and off by phosphorylation reactions performed by protein kinases and phosphatases

Answer 22

E is correct

Question 23

Without checkpoints during the cell cycle, what might happen?

Answer 23

• Mitosis occurs before DNA synthesis
• DNA synthesis without sufficient biochemical preparation (e.g. incomplete/aberrant synthesis)
• Cells cannot enter the G0 state for normal function
  -Daughter cells contain a wrong/different number of chromosomes (aneuploidies)

Question 24

What is prometaphase?

Answer 24

Before metaphase when the nuclear envelope breaks down

Question 25

What would most likely happen if mitosis was not accompanied by cytokinesis?

Answer 25

one cell with two identical nuclei

Question 26

What is Apoptosis? What can suppress apoptosis? What is it mediated by? What signals undergo apoptosis?

Answer 26

It is a system of programmed cell death that multicellular organisms use to get rid of unwanted or damaged cells A number of survival factors (e.g. growth factors and nutrients) could promote cell survival, by suppressing apoptosis It is mediated by an intracellular proteolytic cascade, involves a family of proteases called caspases Both internal and external signals can induce a cell to undergo apoptosis

Question 27

How many pairs of homologous autosomes in a somatic cell? How many sex chromosomes?

Answer 27

22 homologous pairs + 2 sex chromosomes

Question 28

Which division in meiosis is more similar to mitosis? In which division do sister chromatids separate from each other?

Answer 28

Meiosis II; meiosis II Meiosis II resembles mitosis, in which sister chromatids segregate during anaphase II. During meiosis I, the separation of homologous chromosomes occurs. recap lec 10 if unsure

Question 29

How do cells communicate?

Answer 29

Through physical interactions or sending/recieving signalling molecules

Question 30

What is endocrine signalling? Give an example:

Answer 30

* Endocrine cells release signals called hormones that travel through the bloodstream and act on receptors of target cells at distant body sites. ➢ Insulin, produced by pancreatic β-cells, promotes the absorption of glucose into liver, fat and skeletal muscle cells

Question 31

What is Paracrine signalling- Signals that act locally (short distance) What is an example?

Answer 31

* Paracrine signals are released by cells into the extracellular fluid in their neighbourhood and act locally ➢ Nitric Oxide (NO), which acts by relaxing smooth muscle cells around blood vessels, resulting in increased blood flow

Question 32

What is Synaptic signalling?

Answer 32

- Specific signals (neurotransmitters) at specialised junctions (synapses) between nerve cells * Neuronal signals are transmitted electrically along a nerve cell axon. The electrical signal stimulates the nerve terminal to release chemical signals (neurotransmitters) into the synaptic space to reach receptors on adjacent target cells

Question 33

What is Autocrine signalling?

Answer 33

- Signals that act back on the secreting cell * Signalling cells secrete an extracellular signal that binds to receptors on the same cell (signalling cell=target cell) * Usually associated to a feedback response to self-regulate certain cellular processes (e.g. protein secretion) ➢ Cancer cells, produce extracellular signals that stimulate their own survival and proliferation

Question 34

What are the three main stages of cell transduction:

Answer 34

1. Signal-receptor binding 2. Signal transduction 3. Specific cell response

Question 35

Explain Signal-receptor interaction:

Answer 35

*Receptors are proteins that recognise specific ligands (complementary shape) and mediate a response (cell changes/modifies activity) * To respond to a signal, the cells need to posses a receptor for that signal * Each receptor is usually activated by only one type (or a few) of signal(s) * Some signal molecules act at the cell surface whilst others inside the cell (steroids)

Question 36

What are enzyme coupled receptors? (how is receptor cytoplasmic part different?)

Answer 36

Similar to GPCRs, but the receptor cytoplasmic part either: * Acts as an enzyme itself (receptor tyrosine kinases, RTKs) * Or forms a complex with an enzyme

Question 37

What are Receptor tyrosine kinases (RTKs) ?

Answer 37

* Membrane receptors that attach PHOSPHATES to tyrosine amino acids * Can trigger multiple signal transduction pathways at once ➢ Usually, Stimulating cell growth and cell survival ➢ Abnormal functioning of RTKs is associated with many types of cancers

Question 38

Receptor Tyrosine Kinases play a critical role in cell signalling. Describe the step- by-step activation mechanism of Receptor Tyrosine Kinases (RTKs) to intracellularly transduce the signal (5 marks)

Answer 38

1. A specific ligand binds to the RTK extracellularly. 2. This Induces the pairing of 2 RTK receptors (dimerisation) 3. Intracellular receptor parts (kinases) phosphorylate each other's specific tyrosines 4. Phosphorylated tyrosine recruit many different intracellular signalling proteins. 5. Some become phosphorylated and activated (signal transduction), a process required to trigger a complex response such as cell proliferation or differentiation.