Lecture 4 cell signalling Flashcards
Why do cells signal?
Division, growth, differentiation, motility, metabolism, death, secretion and absorption
How do cells signal?
Cell-cell communication via chemical messengers
In what two ways do cells use chemical messengers?
Direct and indirect signalling
What are the two types of direct cell-cell communication?
Gap junctions Juxtracrine signalling (adjacent cells)
What are the 4 types of indirect cell signalling?
Autocrine, paracrine, endocrine and neuronal
What are the 4 types of cell signal?
Hormones
Growth factors
Inflammatory molecules
Neurotransmitters
Give two examples of inflammatory molecules.
Cytokines, prostaglandins
Name 4 neurotransmitters.
Acetylcholine, dopamine, GABA, noradrenaline (norepinephrine)
What are receptors?
Proteins that bind the signal molecule to induce a conformational change
What do intracellular signals cause within a cell?
Fast response: altered protein function
Slow response: altered gene expression
Name some second messenger molecules
Cyclic AMP
Nitric oxide
Cyclic GMP
Lipid metabolites
What are the 4 types of receptor?
Ion channels, G-protein linked receptors, enzymatic receptors and nuclear receptors
Give an example of an ion channel
Nicotinic acetylcholine receptor
Give examples of G-protein-coupled receptors
Adrenoceptors, glucagon receptor
Give an example of enzymatic receptors
Insulin and growth factor receptos
Name 3 examples of nuclear receptors.
Thyroxine, vitamin D and steroid hormone receptors
What is gap junction signalling?
Molecules are exchanged between cells via gap junctions
What proteins make up a gap junction?
2 connexons
What molecules make up a connexon?
6 connexin molecules
What name is given to a single connexon
A hemichannel
What is the ligand involved in juxtacrine signalling?
Plasma membrane of signalling cell A
What is the receptor involved in juxtacrine signalling?
Receptor in plasma membrane of adjacent cell B
Where is juxtacrine signalling important?
Cell migration
In most cases, where is the chemical messenger of indirect signalling secreted into?
Extracellular fluid/lymph/blood
What acts as the ligand during indirect signalling?
The signalling molecule
What does the signalling molecule elicit?
Cellular response in target cell
What is autocrine signalling?
Cell produces a local ligand that acts back on the receptor in the same cell
What does autocrine signalling allow the cell to do?
Sense extracellular environment (acts as biochemical radar)
What is paracrine signalling?
Cell produces a local ligand that acts on neighbouring cells
How do local ligands move during paracrine signalling?
Diffusion across short distances
Give an example of ligands moving via diffusion across short distances in paracrine signalling
Local recruitment of inflammatory cells by mast cells via histamine
What is endocrine signalling
Cell-cell communication over long distances
What are the signalling molecules in endocrine signalling called?
hormones
How are hormones transported?
In circulatory system via blood or lymph
What distances do messages travel in neural signalling?
Nerve impulses travel long distances and chemical messengers travel short distances
What other name is given to the nerve impulses travelling long distances in neural signalling?
Action potentials
What name is given to the travel of signalling molecules in neural signalling?
Synaptic transmission
What is the signalling cell in neural signalling?
The neuron cell
What type of signalling uses neurohormones as ligands?
Neuroendocrine signalling
How long does autocrine signalling take?
msec to sec
How long does paracrine signalling take?
msec to sec
How long does endocrine signalling take?
sec to mins (can be hours to days)
How long does neural signalling take?
msec only
How do hydrophilic signals activate a response?
Activate plasma membrane receptors
How are hydrophobic signals transported around the ECF/blood?
Globular transport proteins
What type of receptors do hydrophobic signal molecules activate?
Intracellular (nuclear) receptors
What classification of signalling molecules do all known hormones (and some neurotransmitters) fall into?
Peptides, amines, steroids
What are the three other classes of signalling molecules, other than peptides, amines and steroids?
Lipids, purines, gases
Are peptides, amines and steroids hydrophobic or hydrophilic?
Either
Purines and gases are hydro___
philic
What type of signalling molecule can single amino acids act as?
Neurotransmitters
What amino acids can act as neurotransmitters?
Asp, Cys, Gly (Glu decarboxylated to form GABA)
What are the two types of single amino acid neurotransmitters?
Excitory amino acids (EAA)
Inhibitory amino acids (IAA)
Peptides (2-200aa) can act as what type of signalling molecules?
Neurotransmitters, hydrophilic hormones
Where are peptides subject to post-translation modifications (e.g. glycosylation)?
Rough ER and golgi apparatus
What signalling molecules are immediately released by exocytosis from their secretory vesicles?
Paracrine peptides- cytokines
What signalling molecules go into storage before being released by exocytosis?
Most peptide hormones and neurotransmitters
Are peptides soluble in ECF/blood/lymph?
Yes- don’t require carrier
What type of hormones does the posterior pituitary release and what type of signalling is this?
Neuroendocrine signalling
Nonapeptide hormones
Give two examples of nonapeptide hormones released by the posterior putuitary
Oxytocin (OT)
Arginine) Vasopressin (AVP
On what receptors do peptides act?
Cell surface/transmembrane receptors
How do peptides act on cell surface/transmembrane receptors?
Conformational change
What is the result of a conformational change of a cell surface or transmembrane receptor in the presence of a peptide ligand?
- Ion flux (iontropic receptor)
- Enzymes (metabotropic receptors)
How are peptides degraded?
Proteases/peptidase
What are the peptide half lifes?
Generally short:
- Secs for simple peptides
- Hours for glycoproteins
What is the consequence of degrading peptide signalling molecules?
Continued action is dependent on continued synthesis
What name is given to organic molecules containing amine (NH2-) usually derived from an aa?
Biogenic amines
What biogenic amines are derived from tyrosine?
Catecholamines
Give an example of catecholamines
Dopamine, noradrenaline and adrenaline
Catecholamines are hydro___
philic
What biogenic enzymes are derived from tyrosine derivatives?
Thyroid hormones
Give an example of a thyroid hormone
Thyroxine
Are thyroid hormones hydrophilic or hydrophobic?
Hydrophobic
What biogenic amines are derived from tryptophan?
Indoleamines
Give two examples of indoleamines
Serotonin and melatonin
What biogenic amine is derived from histidine?
Histamine (hydrophilic)
What biogenic amine is derived from choline (lipid)
Acetylcholine (hydrophilic)
What are steroid hormones derived from?
Cholesterol
How many carbons are there in cholesterol molecules?
27
What class of hormones are steroid hormones?
Endocrine and paracrine hormones
What do steroid hormones do in vertebrates vs invertebrates?
Vertebrates: sex steroids
Invertebrates: ecdysone
What are steroid hormones implicated as?
Phermones for communication
What are the 5 classes of steroid hormones?
Progestins Glucocorticoids Mineralocorticoids Androgens Estrogens
Name a progestin hormone and the number of carbons associated
Progesterone
21C
Name a glucocorticoid and the number of carbon atoms
Cortisol
21C
Name a mineralocorticoid and its number of carbons
Aldosterone, 21C
Name an androgen and the number of carbons it has
Testosterone
19C
Name an estrogen and the number of carbons it has
Estradiol
18C
Where are steroid hormones synthesised?
Mitochondria and smooth ER
What are the implications of steroid hormones being lipophilic?
- Can’t be stored
- Synthesised immediately prior to secretion
What two things do steroids bind?
- Binding globulins
- Albumen
What other hormones binds to carrier proteins, other than steroid hormones?
Thyroid hormones
Vitamin D/cholecalciferol
By what laws do carrier proteins function by?
Laws of mass action and equilibrium
What happens when free messenger enters the target cell and binds to the receptor?
Decreases concentration of free messenger, bound messenger dissociates from carrier protein
What type of receptor do steroid hormones bind?
Nucelar receptors
What are the two classes of nuclear receptor?
Class I nuclear receptor: cytosol
Class II nuclear receptor: nucleus
What do nuclear receptors function as?
Ligand-dependent transcription facotr
What do ligand-dependent transcription factors do?
Bind DNA to control access of RNA polymerase to the DNA template via histone acetylation
What does controlling RNA polymerase access to DNA do?
Modulates transcription of genes in target cells
How fast acting are nuclear receptors in ligand-dependent transcription factors?
Slow acting (hours to days)
What is there increasing evidence for with steroid hormones?
Rapid effects via plasma membrane steroid receptors
