Cell Communication & Signalling Flashcards

1
Q

WWhat is Cell Communication?

A

-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)

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2
Q

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

A
  • 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)
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3
Q

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

A

1) Gap Junctions

2) Anchoring Junctions

3) Tight Junctions

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4
Q

Gap Junctions or communicating junctions, what are they?

A

-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
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5
Q

Diagram of a gap junction?

A
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6
Q

What is cell signalling?

A

-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
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7
Q

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

A

-Contact-Dependent

-Paracrine

-Synaptic

-Endocrine

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8
Q

What is Contact-Dependent cell signalling?

A

-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
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9
Q

What is Endocrine cell signalling ?

A

-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
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10
Q

What is Paracrine cell signalling?

A

-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
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11
Q

What is Synaptic cell signalling?

A

-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
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12
Q

What is Autocrine cell signalling?

A

-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
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13
Q

What are the 3 stages of cell signalling pathway?

A

1) Signal-receptor binding

2) Signal transduction

3) Specific cell response

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14
Q

What does a a Signal Molecule do?

A

-induce different responses in different cells

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15
Q

Upstream/ downstream diagram??

A
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16
Q

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

A

-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)

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17
Q

Signal receptor binding diagrams?

A
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18
Q

What are Intracellular Receptors?

A
  • 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.
19
Q

How a Intracellular receptor works in 5 steps diagram??

A
20
Q

What are the 3 main types of membrane receptors?

A

1) Ion channel-coupled receptors

2) G protein-coupled receptors (GPCRs)

3) Enzyme-coupled receptors

21
Q

What is an Ion channel -coupled receptor?

A

-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

22
Q

What are G proteins- coupled receptors (GPCRs)?

A
  • Largest class of cell-surface receptors
  • G proteins-linked receptors have a common structure, with 2 components
23
Q

What is a Trans-membrane receptor ?

A
  • Trans-membrane protein that crosses 7 times the plasma membrane
  • Ligand binding site is on the extracellular side
24
Q

What is a G- Protein?

A

-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)
25
Q

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

A
26
Q

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

A
27
Q

What is an Enzyme-coupled receptor?

A

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

28
Q

What is a Receptor Tyrosine kinases (RTKs) ?

A
  • 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
29
Q

What does an Enzyme-coupled receptor do?

A
  • 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
30
Q

Enzyme-coupled receptors DIAGRAM

A

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

31
Q

Step 2- Transduction step

A

-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
32
Q

Transduction step - DIAGRAM

A
33
Q

What is the Protein phosphorylation cascade?

A
  • 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.
34
Q

Protein phosphorylation cascade? DIAGRAM

A
35
Q

What is a ‘first messenger’?

A

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

36
Q

What are Second messengers?

A
  • 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
37
Q

Example 1 of Second Messengers in GPCRs
WITH DIAGRAM

A

-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)
38
Q

Example 2 of Second Messengers in GPCRs
WITH DIAGRAM

A

-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
39
Q

Step 3- Cellular response (Signal - receptor interaction)

ADD DIAGRAM

A
  • 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
40
Q

How do cells communicate in multi-cellular organisms?

A

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

41
Q

Most extracellular signal molecules bind to what?

A

-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

42
Q

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

A

1) Ion channel-coupled receptors

2) G-protein-coupled receptors

3) Enzyme-coupled receptors

43
Q

What are the other 2 names of receptors?

A

-There are also cytosolic and nuclear receptors

44
Q

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

A

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