L9 Intercellular Signalling Flashcards
Why do cells need to communicate? [4]
Communication with neighbouring cells
Adaption of metabolism and nutritional requirements to the nutritional state of the body
To induce/decease Growth (division) if the need arises
Respond to danger signals
When new cells are needed, stem cells must… [2]
Upregulate proliferation by the right amount
Differentiation to the desired cell type
Intercellular signalling usually involves… [5]
Synthesis and release of the signalling molecule
Transport of the signalling molecule to the target cell
Detection of the signal by a specific receptor
A change in cellular behaviour triggered by activation of the receptor (activated by intracellular signalling)
Removal of the signal, which often terminates the cellular response. In some cases this may be removal of the receptor.
Types of intercellular signals [4]
Proteins e.g. Interferon, insulin
Peptides e.g. glucagon, growth hormone produced by cleavage of proteins
Small chemicals: steroids, made from cholesterol e.g. estradiol, cortisol
amino acid metabolites e.g. adrenaline, histamine
Dissolved gases e.g. Nitric oxide
For cell to respond to signal, what must happen? [3]
Ligand must be present
Responding cell must have corresponding receptor
Receptor must be correctly coupled to intracellular signalling pathway
Signalling molecule that binds receptor is called…
Ligand
Importance of cell surface receptors [3]
Most signalling molecules are too large/hydrophilic to cross membrane
Ligand binding changes activities of intracellular domains of receptor - initiate response
Signalling molecule does not need to enter cell
Categories of membrane receptors [3]
Receptors linked to ion channels
G protein coupled receptors
Receptors linked to enzymes
Receptors can be located in [2]
cytosol or nucleus
How do small molecules cross?
Small molecules (e.g. Nitric oxide) and hydrophobic molecules(e.g. steroid hormones, thyroxin) can cross the cell membrane and directly bind to receptors in the cytosol or the nucleus
Different responses to the same signal - example?
Different cells responses vary
Adrenaline: Causes SM contraction in BV of gut BUT relaxation of SM in BV of muscles
Opposite actions due to different adrenergic receptors
]
Alpha contract and beta relax in muscles
Muscarinic type
G protein coupled receptor
Nicotinic
Na+/K+ channel
Short range signalling
Endocrine, paracrine, neuronal, autocrine and juxtracrine signalling
Long range signalling
Endocrine
Endrocine signalling - how does it work?
• Hormone: Compound produced by endocrine gland and released into bloodstream
• Acts on target cells at a distance location
• Hormone circulating in blood coming into contact with most cells within body
• Only a limited number of cells can respond to a hormone
• Must express the correct receptor to interpret the signal
Hormones regulate cell reactions by affecting gene expression
Endocrine signalling importance in metabolism
Pancreas: Beta cells = insulin, alpha cells = glucagon
Type 1 diabetes: no insulin
Type 2 diabetes: absent or decreased response to insulin by target cells
Endocrine signalling importance in stress response
The glucocorticoid receptor (GR) can both activate and suppress gene expression producing both metabolic and anti inflammatory effects
Clinical uses of steroids
• Synthetic hormones that activate glucocorticoid receptor: Hydrocortisone, prednisolone and dexamethasone
• Autoimmunity - psoriasis, ulcerative colitis
• Allergic reactions - urticaria
Asthma
Paracrine signalling - how does it work?
• Signalling molecule released from one cell and diffuse locally to neighbouring cell
• Proteins: cytokines (generate immune response) and platelet-derived growth factor (stimulate cell proliferation)
• Amino acid derivative: Histamine promotes local inflammation
Dissolved gas: Nitric oxide relaxes smooth muscle, dilates BVs (arginine derivative)
Nitric oxide and paracrine signalling
NO produced from arg when BV wall endothelial cells are stimulated by Ach
NO diffuses into nearby smooth muscle cells and activates its target enzyme guanylate cyclase
Nitric oxide and cGMP
• NO binds to guanylyl cyclase, and activates it to make cyclic GMP from the nucleotide GTP
• Cyclic GMP causes the smooth muscle cells to relax, and thus increases blood flow through the blood vessel
The effect is short-lived, as the cyclic GMP is quickly hydrolysed to GMP by phosphodiesterase (half-life ~10 seconds)
Angina treatment
Nitroglycerin
Neuronal signalling - how?
Neurotransmitters travel only across the synaptic gap to the adjacent target cell only
Adrenaline: regulates attentiveness and mental focus as neurotransmitter vs blood redirection and glycogen->glucose conversion as a hormone
Neurotransmitter examples [4]
Acetylcholine - released by motor neurons innervating muscle cells
Serotonin - trp derivative and modulates mood
Dopamine - tyr derivative and fine-tuning of motion
Endorphins - peptide (released during pain inducing analgesia)
Autocrine signalling - how?
Cells secrete signalling molecules that bind their own receptors
Many cytokines produced by immune cells can activate the release cell, amplifying activation of that cell which increases cytokine production
Juxtacrine signalling - how?
• Contact-dependent signalling - immediate neighbours signal each other via membrane bound molecules
• Gap junctions - channels form between cells - diffusion of ions, nucelotides and sugars
Contact-dependent receptor ligand binding - direct cell to cell communication/interaction with extracellular matrix
Gap junctions - what are they?
• Gap junctions provide neighbouring cells with a direct communication link that can be opened or closed in response to the cell environment similar to an ion channel
• Gap junctions are formed by channels called connexons
• connexons consist of 6 protein subunits
• 20 types of subunit exist
Connexons can be built from the same or different subunits
Importance of gap junctions
Gap junctions between heart muscle cells allow waves of electrical excitation to pass quickly through the tissue
Gap junctions appear in the myometrium of the uterus towards to the end of pregnancy ,where they help coordinate uterine contractions during childbirth
