Samenvatting
Samenvatting Molecular Biology Of The Cell (006368)
Dit document bevat een samenvatting van de hoorcolleges van het vak 'Molecular biology of the cell' gegeven door professor Luc Leyns aan de Vrije Universiteit Brussel.
[Meer zien]Voorbeeld 4 van de 37 pagina's
Voorbeeld 4 van de 37 pagina's
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Voorbeeld van de inhoud
1. Cell communicationa. Part I: General Principles
Evolution
- Bacteria were present 2.5 billion years before multicellular organisms
- Mechanisms enabling one cell to influence the behavior of another cell were probably already
present in unicellular organisms (e.g. the mating factor in budding yeast)
A simple intracellular signaling pathway
- Signaling molecules are released by signaling cells: signal is a ligand
- Ligand binds to specific receptor on target cell
Signal molecules typically act at low concentrations (< 10-8 M) and receptors have a high
affinity for it
- Ligand – receptor interactions: induce conformational or shape – change in the receptor
- Produces a specific response = cellular response
- Higher organisms: cells use very different type of signal molecules
Proteins, small peptides, amino acids, steroid, retinoids, fatty acid derivatives, nitric oxide
Cell-to-cell communication by extracellular signaling usually involves six steps
- Synthesis of the signaling molecule by the signaling cell
- Release of the signaling molecule by the signaling cell
- Transport of the signal to the target cell
- Detection of the signal by a specific receptor protein – receptor – ligand specificity
- A change in cellular metabolism, function or development = cellular response
Triggered by the receptor-ligand complex
Specific to the ligand-receptor complex
Specific to the responding cell
- Removal of the signal which usually terminates the cellular response – degradation of ligand
Binding to cell-surface or intracellular receptor
- Cell surface receptors
Hydrophilic molecules are the signals: binds to cell-surface receptor
- Intracellular receptors
Small hydrophobic signal molecule transported by carrier protein and can then cross the
membrane (without carrier protein): attach to intracellular receptor
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,Extracellular signals can act over long or short distances
- Contact-dependent
- Paracrine: uses local mediators to send messages from signaling cell to the target cell
Signal molecules are released into the surrounding fluids and then diffuse into nearby cells
Endocrine signaling: long distances – slow
- Releases hormones into blood stream
- Hormones are carried to the appropriate target cells
- Every target cell has a receptor
- Endocrine signaling is used when the transportation distance exceeds the ability of diffusion
Synaptic signaling: long distances – fast
- Neurons connect through synapses = small gaps between neurons
- Chemical substances are released from the pre-synaptic neuron to affect the post synaptic
neuron
- Post synaptic neurons have receptors that these chemical substances bind to
- Neuron can connect to other cells as well as to other neurons
- Long axons: neurotransmitter at end
- Fast due to electrical nature
Autocrine signaling
- Cell secretes signal molecules that bind to its own receptors
- Starting cell will trigger collective response
- Community effect: performed by a group of cells
- Used by cancer cells: produces own growth signals
Gap junctions allow sharing of signaling information
- Connection between 2 cells: allow exchange of small molecules (Ca2+, cAMP)
Each cell is programmed to respond to specific combination of signals
- Survive
- Divide
- Differentiate
- Die: apoptosis
2
,Different cells can respond differently to the same signal
- E.g. acetylcholine
Heart muscle cell: decrease rate and force of contractions
Skeletal muscle cell: contraction
Salivary gland cell: secretion of saliva
Adjustment of the concentration of a signaling molecule
- Signal leads to changes
- Development: even when the signal is removed, the changes persist
- Adults: response generally fades when the signal disappears
- Generally signal is transient because it alters unstable molecules undergoing continuous
turnover
- Speed of cellular response to signal removal depends on turnover rate
Nitric oxide (NO)
- Diffuses to neighboring cells
- Binds to an intracellular enzyme
- In mammals: regulates smooth muscle contractions
NO gas produced by deamination of arginine catalyzed by NO synthase
Dissolved NO diffuses quickly
NO binds to iron in active site of guanylyl cyclase: forming of cGMP
Rapid relaxation of smooth muscle cell
Half-life is 5-10 seconds
cGMP has a high turnover because it is degraded by a cGMP phosphodiesterase
effect occurs in seconds: Viagra inhibits the cGMP phosphodiesterase in the penis therefore
cGMP level remains high longer, the blood vessels stay relaxed and more blood is coming
Nuclear receptors are ligand-activated gene regulatory proteins
- Some signal molecules are small hydrophobic molecules that can cross the cell membrane and
bind to intracellular receptor proteins
- Water-insoluble molecules persist generally longer than soluble ones and mediate generally
responses that last longer
Nuclear receptor superfamily
- After binding to the ligand, the receptors will bind to DNA to regulate the transcription of
specific genes
- Receptors structurally related: superfamily
Have DNA binding domain, ligand binding domain
- Ligand unknown for many receptors: ‘orphan ligands’
3
, Hydrophobic molecules: hormones
- Transported in blood via carrier proteins
- Diffusion intro cells
- Inactive nuclear receptor: present in cytosol, present in nucleus
- Binds as homo- or heterodimer to DNA
- Inactive receptor is located in the cytoplasm (and then migrate to the nucleus) or is already
present in the nucleus
- Gene activation often depends on more than one signal
Three large classes of cell-surface receptor proteins
- Bind water-soluble signal molecules
- Act as signal transducers by converting an extracellular signal in an intracellular one
Ion-channel-linked receptors
G-protein-linked receptors
Enzyme-linked receptors
Intracellular signaling molecules
- Signal is relayed intracellulary to lead ultimately to alteration in target proteins
- Small intracellular mediators (second messengers)
Generated in large number, diffuses from the source and broadcast the signal to other part
of the cell
cAMP of Ca2+
Intracellular signalling proteins
- Extracellular signal molecules bind to receptor
- Scaffold protein: ensures that proteins are positioned locally: ready to answer quickly
- Amplifier: amplification of the signal: multiple effects
Contrary: nuclear: no amplifier!
- Small intracellular mediator: e.g. cyclic AMP, cyclic GMP…
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