Cell Communication & Signalling

Question 1

WWhat is Cell Communication?

Answer 1

-It governs basic cellular functions and coordinates activities within and among tissues/organs of multicellular organisms, in response to external changes

-Cells communicate through physical interactions or sending/receiving signalling molecules (CELL SIGNALLING)

Question 2

What is Stable Cell- Cell Interactions (physical communication)?

Answer 2

• Required for cell adhesion within a tissue
• Controlling the shape and function of cells
• Organisation of cells into tissues (e.g Epithelia)
• Required for anchoring cell in the ExtraCellular Matrix or ECM (space between cells composed a meshwork of proteins and polysaccharides secreted by cells)

Question 3

There are three types of junctions (multi protein complexes) mediating cell-cell or cell-ECM, what are they?

Answer 3

1) Gap Junctions

2) Anchoring Junctions

3) Tight Junctions

Question 4

Gap Junctions or communicating junctions, what are they?

Answer 4

-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

• ONLY GAP JUNCTIONS provide direct communication or material exchange between cells.
• Allowing direct and bidirectional exchange of molecules/ions between 2 neighbour cells

-Heart (cardiac muscle): to pass the signal to contract

• No effect in cell -ECM adhesions

Question 5

Diagram of a gap junction?

Question 6

What is cell signalling?

Answer 6

-The signalling cell produces a type of extracellular signal molecule that is detected by the target cell (specific receptors)

• Target cells possess proteins called receptors that specifically recognise the signal molecule
• Signals can act over a long or short range

Question 7

What are the 4 main ways of transient cell communication/cell signalling ?

Answer 7

-Contact-Dependent

-Paracrine

-Synaptic

-Endocrine

Question 8

What is Contact-Dependent cell signalling?

Answer 8

-signals between interacting cells (2 ways)

• 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 9

What is Endocrine cell signalling ?

Answer 9

-signals (hormones) to act on distant cells/districts

• Endocrine cell releases signals called hormones that travel through the bloodstream and act on receptors of target cells at distant body sites
• Insulin, produced by pancreatic beta cells, promotes the absorption of glucose into liver, fat and skeletal muscle cells

Question 10

What is Paracrine cell signalling?

Answer 10

-signals that act locally (short distance)

• 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 the blood vessels, resulting in increased blood flow

Question 11

What is Synaptic cell signalling?

Answer 11

-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 12

What is Autocrine cell signalling?

Answer 12

-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 13

What are the 3 stages of cell signalling pathway?

Answer 13

1) Signal-receptor binding

2) Signal transduction

3) Specific cell response

Question 14

What does a a Signal Molecule do?

Answer 14

-induce different responses in different cells

Question 15

Upstream/ downstream diagram??

Question 16

STEP 1- Signal binding - Receptor interaction, what is it?

Answer 16

-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 signals. Some signal molecules act at the cell surface whilst others inside the cell (steroids)

Question 17

Signal receptor binding diagrams?

Question 18

What are Intracellular Receptors?

Answer 18

• Some receptor proteins are intracellular, found in the cytosol or nucleus of target cells.
• Small/hydrophobic signal molecules can readily cross the membrane and activate receptors e.g. steroids (cortisol, estradiol, testosterone), thyroid hormones (thyroxine)
• A hormone receptor complex can act as a transcription factor, binding DNA sequences, to modify the transcription level of specific genes to produce effector proteins.

Question 19

How a Intracellular receptor works in 5 steps diagram??

Question 20

What are the 3 main types of membrane receptors?

Answer 20

1) Ion channel-coupled receptors

2) G protein-coupled receptors (GPCRs)

3) Enzyme-coupled receptors

Question 21

What is an Ion channel -coupled receptor?

Answer 21

-The receptor conformational change after binding up 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)

-E.g Nerve cells and other electrically excitable cells such as muscle

Question 22

What are G proteins- coupled receptors (GPCRs)?

Answer 22

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

Question 23

What is a Trans-membrane receptor ?

Answer 23

• Trans-membrane protein that crosses 7 times the plasma membrane
• Ligand binding site is on the extracellular side

Question 24

What is a G- Protein?

Answer 24

-G protein (acts as an on/off switch)

• On the cytosolic side of the plasma membrane
• 3 protein subunits alpha, beta, (y)
• A subunit is associated with GDP (inactive state)
• Ligand binding activities a (alpha) subunit that exchanges GDP for GTP (active state)

Question 25

G Proteins-coupled receptor (GPCRs) - Activation Diagram??

Question 26

G Proteins-coupled receptor (GPCRs) effect and inactivation DIAGRAM??

Question 27

What is an Enzyme-coupled receptor?

Answer 27

-Acts as an enzyme itself (receptor tyrosine kinases, RTKs) or forms a complex with an enzyme

Question 28

What is a Receptor Tyrosine kinases (RTKs) ?

Answer 28

- 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 29

What does an Enzyme-coupled receptor do?

Answer 29

- Ligand binding induces the pairing of 2 receptors (dimerisation) - Intracellular receptor parts (kinases) phosphorylate each others specific tyrosines - Phosphorylated tyosine recruit many different intracellular signalling proteins - Some become phosphorylated and activated (signal transduction ), a process required to trigger a complex response such as a cell proliferation or differentiation

Question 30

Enzyme-coupled receptors DIAGRAM

Answer 30

-The effect is reversed by phosphatases removing the phosphates from the tyrosines

Question 31

Step 2- Transduction step

Answer 31

-Multisteps to amplify a signal - Multistep pathways provide more opportunities for co ordination and regulation - Different transduction strategies (phosphorylation cascade or second messengers) for different pathways

Question 32

Transduction step - DIAGRAM

Question 33

What is the Protein phosphorylation cascade?

Answer 33

- the signal is transduced by a protein phosphorylation cascade - This phosphorylation (by kinases) and dephosphorylation (by phosphatases) system acts as a molecular switch, turning activities on and off.

Question 34

Protein phosphorylation cascade? DIAGRAM

Question 35

What is a 'first messenger'?

Answer 35

-The binding of an extracellular signal molecule to the membrane receptor activates enzymes, which is a pathway’s ‘first messenger’

Question 36

What are Second messengers?

Answer 36

- Second messengers can readily spread through cells to amplify the signal - Second messengers are small, non protein, water soluble molecules or ions -cAMP (cyclic AMP), cGMP (cyclic GMP), lipids, Ca2+, NO (nitrogen monoxide) - Second messengers participate in pathways initiated by GPCR and RTK

Question 37

Example 1 of Second Messengers in GPCRs WITH DIAGRAM

Answer 37

-Activation of some G-protein-linked receptors can activate a membrane-bound enzyme called adenylyl cyclase that converts ATP to cAMP - cAMP exerts most of its effects by activating the enzyme cyclic-AMP-dependent protein kinase (PKA) - Activated PKA catalyses the phosphorylation of particular serines/threonines on specific target proteins (e.g. involved in the glycogen breakdown)

Question 38

Example 2 of Second Messengers in GPCRs WITH DIAGRAM

Answer 38

-Another membrane-bound enzyme associated to GPCRs is phospholipase C. Once activated, it cleave a lipid generating 2 small molecules called inositol triphosphate (IP3) and diacylglycerol - IP3, opens Ca2+ channels in the endoplasmic reticulum to release Ca2+ (2nd messenger) in the cytosol - Ca2+ activates many proteins triggering many biological processes

Question 39

Step 3- Cellular response (Signal - receptor interaction) ADD DIAGRAM

Answer 39

- Cell signalling ultimately leads to the regulation of one or more cellular activities - Regulation of gene expression (turning transcription of specific genes on or off) is a common outcome

Question 40

How do cells communicate in multi-cellular organisms?

Answer 40

-Cells in multi cellular organisms communicate through a variety of extracellular chemical signals between adjacent cells as well as over short and long distances

Question 41

Most extracellular signal molecules bind to what?

Answer 41

-cell-surface receptor proteins that convert (transduce) the extracellular signal into different intracellular signals, which are usually organised into signalling pathways and trigger specific cellular responses

Question 42

There are three main classes of cell-surface receptors, what are they?

Answer 42

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

Question 43

What are the other 2 names of receptors?

Answer 43

-There are also cytosolic and nuclear receptors

Question 44

What happens after signal-receptor binding (first messenger)?

Answer 44

-the signal is transduced into different forms and involving multiple steps (e.g. phosphorylations cascade or types of second messengers)