Tijmen Lourens Summary Cell Biology and Immunology
Cell Biology and Immunology
Lecture 1A: cell signalling
General principles of cell signalling:
- Cell surface receptors:
o Ion-channel-coupled receptors
o G-protein-coupled receptors
o Enzyme-coupled receptors
- Cells need to sense and responds to their environment
- Signals: nutrients, light, predators, poisons etc
- Multicellular organisms: also communication between cells
→ how cells send signals and interpret the signals they receive?
Cells communicate by means of numerous kinds of signal molecules
Communication involves converting the information signals from one form to another (signal
transduction)
The Signalling Cell: produces a particular type of signal molecule
The Target Cell: detects that particular signal molecule
There are 4 ways of cell communication:
- Contact-dependent
o Short distance
o Direct contact (like face-to-face conversation)
o Important for embryonic development and in immune response
- Paracrine
o Local diffusion of a signal
o Signal molecules: local mediator on nearby cells
o Animal cells that produce mediators are called: paracrine cells
o Example: molecules that regulate inflammation at site of infection
- Synaptic
o Long distance, quick and highly specific communication (like phone call)
▪ Signal molecules: neurotransmitters
▪ Secreted at nerve terminal (regulated exocytosis)
▪ Produces by neurons
o long distance: > 1 meter → spinal cord to toes
o speeds of up to 100 m/sec via electrical impulses along axon
- endocrine
o ‘public’ style of communication (like broadcasting over a radio station): signal
throughout the whole body upon secretion in animal bloodstream or a plant’s
sap
▪ Signal molecules: hormones
▪ Animal cell that produces hormones: endocrine cells
▪ Example: insulin
,Tijmen Lourens Summary Cell Biology and Immunology
The effect of the signal can be fast or slow: photo
- Cell contraction: very fast → able to walk/move
- Growth and division: much slower, goes via the nucleus with DNA and RNA
Signal molecules:
- Proteins
- Peptides
- Amino acids
- Nucleotides
- Steroids
- Fatty acid derivatives
- Dissolved gases
o BUT: only a handful of basic styles of communication for getting the message
across
Many signal molecules act at very low concentrations (< 10^-8 M)
Receptors bind them with high affinity (dissociation constant Kd <10^-8 M)
Cells depend on different signals: PHOTO
Different cell types can respond differently to the same extracellular signal
The response of a cell to an extracellular signal depends on:
- Receptor proteins
- Intracellular signalling processing machinery → PHOTO
Two major types of extracellular signal molecules:
First type:
- Large and hydrophilic
- Need cell surface receptors
- E.g., insulin, growth factors (peptides/proteins)
o Recognized by cell surface-receptor proteins:
▪ Ion-channel-coupled receptors
▪ G-protein-coupled receptors
▪ Enzyme-coupled receptor
Second type:
- Small and hydrophobic
- Intracellular receptors
- E.g., steroid hormones
o Recognized by nuclear receptors:
▪ Inside the nucleus
▪ Nuclear receptor not always inside the nucleus but they function in
the nucleus → through nuclear envelope
▪ Goes in ‘active’ form when for example cortisol couples
▪ Produces a lot of mRNA → transcription of target gene
- Other examples of compounds that bind to nuclear receptors:
o Cortisol, estradiol, testosterone, vitamin D3, thyroxine, retinoic acid:
▪ All small and hydrophobic
,Tijmen Lourens Summary Cell Biology and Immunology
Lecture 1B: the three major classes receptors
- Ion-channel-coupled receptors
o Change in permeability of membrane to selected ions
o Change in membrane potential
▪ Protein binds to channel → channel opens; THAT IT!
• Protein kinases play important roles
- G-protein-coupled receptors
o Activate G-protein: trimeric GTP binding protein
o This activates enzyme or ion channel, which initiates further signalling
cascade (second messenger)
- Enzyme-coupled receptors
o Signal molecules cause dimerization of receptor
o Dimeric receptor is the enzymatically active form of the receptor
o The active receptor activates another enzyme, which in turn activates a wide
variety of intracellular signalling pathways
G-protein-coupled receptors: GPCRs
- Form the largest family of cell surface receptors
- > 800 GPCRs in humans
- Our senses of sight, smell and taste depends on them
- > 1000 in mice only for smell
- Signal molecules that they sense: proteins, small peptides, derivatives of amino acids
and fatty acids etc.
- About one third of all drugs work through GPSRs.
o All GCPRs have similar structure: a single polypeptide that goes 7 times
through the plasma membrane
Activation of g-protein:
- Dissociation into active subunits
o Activated alpha subunit activates a target protein
o Target protein can be an enzyme or ion channel
o GTP hydrolysis results in inactivation of the G protein
Some G-proteins activate membrane-bound enzymes
- Enzymes activated by G proteins catalyse the production of small intracellular
signalling molecules → second messengers
o Adenylyl cyclase (produces cAMP)
▪ Phospholipase C (generates inositol triphosphate and diacylglycerol)
▪ cAMP is synthesized by adenylyl cyclase and degraded by cAMP
phosphodiesterase
• caffeine as stimulant inhibits cAMP phosphodiesterase
o → cAMP levels stay high
• cAMP-dependent protein kinase, phosphorylates mainly
metabolic enzymes
, Tijmen Lourens Summary Cell Biology and Immunology
Enzyme-coupled receptors:
- transmembrane proteins
- cytosolic domain acts as enzyme or forms complex with an enzyme
- signal proteins generally local mediators that act at low concentrations
- relatively slow response
- generally leads to change in gene expression
- largest class are receptor tyrosine kinases → RTKs
receptor activation by forming a dimer, followed by trans-phosphorylation
Signalling path growth factor receptors via RAS, part 1:
- Ras:
o Small GTP binding protein, bound by lipid tail to plasma membrane
o Monomeric GTPase and molecular switch
o Initiates phosphorylation cascade
o Activating mutations cause cancer
Signalling path growth factor receptors via RAS< part 2:
- PHOTO:
o MAP: mitogen activated protein kinase
o Mitogens stimulate cell division
Cell signalling: key points
- Cells communicate through variety of extracellular chemical signals
- Extracellular signals stimulate a target cell when they bind to and activate receptor
proteins
- There are 3 main classes of cell surface receptors (ion channel coupled / GPCRs /
enzyme-coupled
- Turning off signalling pathway is as important as turning it on
- GPCRs activate G-proteins, these act as molecular switches and transmit the signal
onwards and turning them off
- G-proteins can directly activate ion channels on the membrane or enzymes that are
bound to the membrane
Lecture 2A: general properties of the cytoskeleton
3 types of protein filaments:
1) Actin filaments → movement ± 509 nm
2) Microtubules → intracellular organization ± 25 nm
3) Intermediate filaments → mechanical strength (shape nucleus!) ± 10 nm
Cytoskeleton:
- Network of protein filaments
- Supports large volume of the cytoplasm
- Highly dynamic
- Functions as ‘bones’ and ‘muscles’
o Cell movement, muscle contraction, changes in cell shape, swimming of
sperm cells
Cell Biology and Immunology
Lecture 1A: cell signalling
General principles of cell signalling:
- Cell surface receptors:
o Ion-channel-coupled receptors
o G-protein-coupled receptors
o Enzyme-coupled receptors
- Cells need to sense and responds to their environment
- Signals: nutrients, light, predators, poisons etc
- Multicellular organisms: also communication between cells
→ how cells send signals and interpret the signals they receive?
Cells communicate by means of numerous kinds of signal molecules
Communication involves converting the information signals from one form to another (signal
transduction)
The Signalling Cell: produces a particular type of signal molecule
The Target Cell: detects that particular signal molecule
There are 4 ways of cell communication:
- Contact-dependent
o Short distance
o Direct contact (like face-to-face conversation)
o Important for embryonic development and in immune response
- Paracrine
o Local diffusion of a signal
o Signal molecules: local mediator on nearby cells
o Animal cells that produce mediators are called: paracrine cells
o Example: molecules that regulate inflammation at site of infection
- Synaptic
o Long distance, quick and highly specific communication (like phone call)
▪ Signal molecules: neurotransmitters
▪ Secreted at nerve terminal (regulated exocytosis)
▪ Produces by neurons
o long distance: > 1 meter → spinal cord to toes
o speeds of up to 100 m/sec via electrical impulses along axon
- endocrine
o ‘public’ style of communication (like broadcasting over a radio station): signal
throughout the whole body upon secretion in animal bloodstream or a plant’s
sap
▪ Signal molecules: hormones
▪ Animal cell that produces hormones: endocrine cells
▪ Example: insulin
,Tijmen Lourens Summary Cell Biology and Immunology
The effect of the signal can be fast or slow: photo
- Cell contraction: very fast → able to walk/move
- Growth and division: much slower, goes via the nucleus with DNA and RNA
Signal molecules:
- Proteins
- Peptides
- Amino acids
- Nucleotides
- Steroids
- Fatty acid derivatives
- Dissolved gases
o BUT: only a handful of basic styles of communication for getting the message
across
Many signal molecules act at very low concentrations (< 10^-8 M)
Receptors bind them with high affinity (dissociation constant Kd <10^-8 M)
Cells depend on different signals: PHOTO
Different cell types can respond differently to the same extracellular signal
The response of a cell to an extracellular signal depends on:
- Receptor proteins
- Intracellular signalling processing machinery → PHOTO
Two major types of extracellular signal molecules:
First type:
- Large and hydrophilic
- Need cell surface receptors
- E.g., insulin, growth factors (peptides/proteins)
o Recognized by cell surface-receptor proteins:
▪ Ion-channel-coupled receptors
▪ G-protein-coupled receptors
▪ Enzyme-coupled receptor
Second type:
- Small and hydrophobic
- Intracellular receptors
- E.g., steroid hormones
o Recognized by nuclear receptors:
▪ Inside the nucleus
▪ Nuclear receptor not always inside the nucleus but they function in
the nucleus → through nuclear envelope
▪ Goes in ‘active’ form when for example cortisol couples
▪ Produces a lot of mRNA → transcription of target gene
- Other examples of compounds that bind to nuclear receptors:
o Cortisol, estradiol, testosterone, vitamin D3, thyroxine, retinoic acid:
▪ All small and hydrophobic
,Tijmen Lourens Summary Cell Biology and Immunology
Lecture 1B: the three major classes receptors
- Ion-channel-coupled receptors
o Change in permeability of membrane to selected ions
o Change in membrane potential
▪ Protein binds to channel → channel opens; THAT IT!
• Protein kinases play important roles
- G-protein-coupled receptors
o Activate G-protein: trimeric GTP binding protein
o This activates enzyme or ion channel, which initiates further signalling
cascade (second messenger)
- Enzyme-coupled receptors
o Signal molecules cause dimerization of receptor
o Dimeric receptor is the enzymatically active form of the receptor
o The active receptor activates another enzyme, which in turn activates a wide
variety of intracellular signalling pathways
G-protein-coupled receptors: GPCRs
- Form the largest family of cell surface receptors
- > 800 GPCRs in humans
- Our senses of sight, smell and taste depends on them
- > 1000 in mice only for smell
- Signal molecules that they sense: proteins, small peptides, derivatives of amino acids
and fatty acids etc.
- About one third of all drugs work through GPSRs.
o All GCPRs have similar structure: a single polypeptide that goes 7 times
through the plasma membrane
Activation of g-protein:
- Dissociation into active subunits
o Activated alpha subunit activates a target protein
o Target protein can be an enzyme or ion channel
o GTP hydrolysis results in inactivation of the G protein
Some G-proteins activate membrane-bound enzymes
- Enzymes activated by G proteins catalyse the production of small intracellular
signalling molecules → second messengers
o Adenylyl cyclase (produces cAMP)
▪ Phospholipase C (generates inositol triphosphate and diacylglycerol)
▪ cAMP is synthesized by adenylyl cyclase and degraded by cAMP
phosphodiesterase
• caffeine as stimulant inhibits cAMP phosphodiesterase
o → cAMP levels stay high
• cAMP-dependent protein kinase, phosphorylates mainly
metabolic enzymes
, Tijmen Lourens Summary Cell Biology and Immunology
Enzyme-coupled receptors:
- transmembrane proteins
- cytosolic domain acts as enzyme or forms complex with an enzyme
- signal proteins generally local mediators that act at low concentrations
- relatively slow response
- generally leads to change in gene expression
- largest class are receptor tyrosine kinases → RTKs
receptor activation by forming a dimer, followed by trans-phosphorylation
Signalling path growth factor receptors via RAS, part 1:
- Ras:
o Small GTP binding protein, bound by lipid tail to plasma membrane
o Monomeric GTPase and molecular switch
o Initiates phosphorylation cascade
o Activating mutations cause cancer
Signalling path growth factor receptors via RAS< part 2:
- PHOTO:
o MAP: mitogen activated protein kinase
o Mitogens stimulate cell division
Cell signalling: key points
- Cells communicate through variety of extracellular chemical signals
- Extracellular signals stimulate a target cell when they bind to and activate receptor
proteins
- There are 3 main classes of cell surface receptors (ion channel coupled / GPCRs /
enzyme-coupled
- Turning off signalling pathway is as important as turning it on
- GPCRs activate G-proteins, these act as molecular switches and transmit the signal
onwards and turning them off
- G-proteins can directly activate ion channels on the membrane or enzymes that are
bound to the membrane
Lecture 2A: general properties of the cytoskeleton
3 types of protein filaments:
1) Actin filaments → movement ± 509 nm
2) Microtubules → intracellular organization ± 25 nm
3) Intermediate filaments → mechanical strength (shape nucleus!) ± 10 nm
Cytoskeleton:
- Network of protein filaments
- Supports large volume of the cytoplasm
- Highly dynamic
- Functions as ‘bones’ and ‘muscles’
o Cell movement, muscle contraction, changes in cell shape, swimming of
sperm cells
