Cell Signalling Flashcards
Why do cells signals?
- Growth
- Differentiation
- Motility
- Metabolism
- Division
- Absoption
- Secretion
- Death
In order to do any of these things communication is key
How can cells communicate?
- direct and indirect
What are the direct ways to signal?
- Gap junctions
- Juxtacrine signalling (adjacent)
What are the indirect ways to signal?
- autocrine signalling (self)
- paracrine signalling (neighbouring)
- endocrine (at a distance - blood)
- neuronal signalling (at a distance - neurons)
What are the different ways cells signal?
- hormones (adrenaliine, insulin, testosterone)
- growth factors (insulin-like growth factors)
- inflammatory molecules (cytokines, prostaglandins)
- neurotransmitters (acetylcholine, dopamine, GABA, noradrenaline)
How are the signals received?
- Receptors
- proteins that bind to the signal molecule to induce a conformational change
What are the type of receptors?
- Ion channels (e.g. nicotinic acetylcholine receptor)
- G-protein-coupled receptors (GPCR)
(e. g. adrenoceptors, glucagon receptor) - Enzymatic receptors (e.g. insulin and growth factor receptors)
- Nuclear receptors (e.g. thyroxine, vitamin D and steroid hormone receptors)
Direct methods: What is gap junction signalling?
- Molecules exchanged between cells via gap junctions:
6 connexin molecules form a connexon
2 connexons form a gap junction (channel)
Direct methods: What is juxtacrine signalling?
- Ligand in plasma membrane of signalling cell A (e.g. ephrin)
- Receptor in plasma membrane of adjacent target cell B (e.g. eph receptor)
- important for cell migration
What is indirect signalling?
- Signalling cell produces a chemical messenger / signalling molecule
- In most cases, signalling molecule secreted into ECF / lymph / blood
- Signalling molecule transported over distance (short, medium or long) to target cell
- Signalling molecule acts as ligand for receptor on / in target cell
- Signalling molecule elicits cellular response in target cell
Indirect methods: What is autocrine signalling?
- Cell produces a local ligand that acts back on the receptor in the same cell!
- Allows cell to sense extracellular environment (“biochemical radar”)
Indirect methods: What is paracrine signalling?
- Cell produces a local ligand that acts on neighbouring cells
- Moves over short distances by diffusion (e.g. local recruitment of inflammatory cells by mast cells via histamine)
Indirect methods: What is endocrine signalling?
- Cell-cell communication over long distances
- Signalling cell termed an endocrine cell
- Signalling molecules (hormones) transported in circulatory system – blood (or lymph)
Indirect methods: What is neural signalling?
- Messages (nerve impulses) travel long distances but chemical messengers only travel short distances:
- Long distances – action potentials
- Synaptic transmission – signalling molecules
What is the speed of communication for autocrine?
- shortest distance – msec to sec
What is the speed of communication for paracrine?
- short distance – msec to sec
What is the speed of communication for endocrine?
- long distance – sec to mins (can be hours to days!)
What is the speed of communication for neural?
- long distance – msec only!
What are some biophysical properties?
- Hydrophilic:
- soluble in aqueous solutions (ECF / blood / lymph)
- activate plasma membrane receptors
- Hydrophobic:
- insoluble in aqueous solutions (soluble in lipids / lipophilic)
- require globular transport proteins to solubilise in ECF / blood
- activate intracellular (nuclear) receptors
What are the 6 major classes of signalling molecules?
- peptides: hydrophilic
- amines: either
- steroids: hydrophobic
- lipids: hydrophobic
- purines: hydrophilic
- gases: hydrophilic
What are the 3 major classes of all known hormones?
- peptides
- amines
- steroids
What are peptides?
- Single amino acids act as neurotransmitters (e.g. Asp, Cys, Glu – latter decarboxylated to form GABA) – can be excitatory amino acids (EAA) or inhibitory amino acids (IAA)
- Peptides (2-200 aa) act as:
- Neurotransmitters (e.g. endorphins [16/17/31 aa])
- Hydrophilic hormones (e.g. endorphins [16/17/31 aa], oxytocin [9 aa] and TRH [3 aa])
…. peptides?
- Translated from mRNA in rough ER
- Subject to post-translation modifications (e.g. glycosylation) in rough ER and Golgi apparatus
- Packaged into secretory vesicles – released by exocytosis (membrane depolarisation)
- Immediate (paracrine peptides – cytokines)
- Storage (most peptide hormones & neurotransmitters)
- Soluble in ECF / blood / lymph – don’t require a carrier / transport protein
What are some nonapeptide hormones?
Posterior pituitary nonapeptide hormones:
Oxytocin (OT)
(Arginine) Vasopressin (AVP)
…. peptides?
- Act via cell surface / transmembrane receptors: conformational change – affects:
- ion flux (ionotropic receptor)
- enzymes (metabotropic receptors)
- Degraded by action of proteases / peptidases – dictates peptide ‘half-life’; generally short:
- secs for simple peptides (e.g. TRH)
- hours for glycoproteins (e.g. LH & hCG)
- Consequence: continued action dependent on continued synthesis
What are biogenic amines?
Organic molecules containing amine (NH2) – usually derived from an amino acid
What are steroid hormones?
- Derived from cholesterol – hydrophobic 27C
- Important class of endocrine / paracrine hormones in all vertebrates (e.g. sex steroids) and many invertebrates (e.g. ecdysone)
- Implicated as pheromones for communication
What are the 5 classes of steroid hormone?
- Progestins (e.g. progesterone) – 21C
- Glucocorticoids (e.g. cortisol) – 21C
- Mineralocorticoids (e.g. aldosterone) – 21C
- Androgens (e.g. testosterone) – 19C
- Estrogens (e.g. estradiol) – 18C
- Synthesised in mitochondria + smooth ER
- Lipophilic:
- Can’t be stored
- Synthesised immediately prior to “secretion”
How do steroid hormones function?
Steroids bind:
- Binding globulins (e.g. CBG and SHBG)
- Albumen
- Same principle applies to thyroid hormones (and Vitamin D/cholecalciferol)
Carrier proteins function by laws of mass action & equilibrium M + C M-C M = messenger C = carrier M-C = messenger-carrier complex
How do Steroid hormones function?
Classically bind “nuclear” receptors
- cytosol (class I nuclear receptor)
- nucleus (class II nuclear receptor)
Functions as ligand-dependent transcription factor – binds DNA – controls access of RNA polymerase to DNA template (via histone acetylation) – modulates transcription of genes in target cell – slow acting (hours to days)
Increasing evidence for rapid effects via plasma membrane steroid receptors (e.g. mitogenic effects of estrogens)
