Lecture 13 - Principles of Cell Communication Flashcards
In multicellular organisms, cells must communicate to
Organise themselves into a functioning unit
Cells sending signals must be able to
Control the signals
Cells receiving signals must be able to
Interpret the information accurately
Communication is mediated by
Extracellular signalling molecules
Signalling molecules can
Interact with receptor molecules in the plasma membrane
The receptors in the plasma membrane
Transmit the signal inside the cell to activate a signalling cascade
What can a signalling cascade do? (4)
Changes enzymatic activity
Metabolism
Gene expression
Induce rearrangements of the cytoskeleton (movement etc.)
Signal transduction
When the signal is transmitted into a cell
Effector molecules alter the
Behaviour of the cell in response to a signal
Examples of signalling molecules
Nucleotides (cAMP, NADPH) Adrenalin (small molecules) Oestrogen (steroids) Insulin (proteins and peptides) Mal-CoA (fatty acids) Nitirc oxide (dissolved gases
Nitric oxide
Is used as a signal to relax smooth muscle in blood vessels
Increases blood flow
How viagra works
Inhibits phosphodiesterase Type 5 from degrading cGMP
NO signalling
- NO synthase upregulated
- Smooth muscle cells activate Guanylyl Cyclase
- Guanylyl cyclase produces more cGMP
- Blood flow is increased as vessels relax
Extracellular signals can act over
Long or short distances
Cell signalling is mediated by
Contacts with the target cell
The 5 ways of getting a signal to the right place
- Contact dependent
- Paracrine
- Synaptic
- Endocrine
- Gap junctions
Contact dependent cell signalling
Via membrane bound receptors and membrane bound signalling molecules
Important in immune response and development
Involved in determining cell fate
Paracrine cell signalling
Release of signalling molecules into the extracellular fluid
Acts locally only
Rapidly taken up and sequestered/destroyed by neighbouring cells
Synaptic cell signalling
Chemical secreted across a space as a result of an electrical impulse
Short range (from perspective of cell-cell contact) Long range (due to of length of cell) Fast Specific High concentrations Low affinity
Endocrine cell signalling
Long range signalling to distant cells
Hormones secreted into the bloodstream Specific Highly dilute Low concentrations High affinity
Gap junction cell signalling
Direct communication between neighbouring cells
Narrow cytoplasmic filled channels
Exchange of ions and small molecules (Ca2+, cAMP)
Directionality of signal (not all cells have GJ)
Connexins
6 subunit protein that forms GAP junctions (small channels in cell membranes)
Twist open or closed
Gap junctions are important in cell signalling in
The heart (Ca2+) The bones (cells surrounded by bone supplied by nutrients by GJ)
Extracellular signals are communicated inside the cell by (2)
- Directly - signal passes into cell (steroids, GJ)
2. Indirectly - binds a receptor, induces conformational change
Signalling inside the cell: Ion channel coupled (indirect)
Rapid synaptic signalling
Muscle cells
Gated channels (conformational change as charged residues are removed, allowing ion influx)
Signalling inside the cell: G protein coupled (GPCRs)
Receptors have 7 transmembrane domains (serpentine)
Ligand binds, complexes with trimeric G proteins (alpha beta gamma subunits)
Activate an enzyme at the plasma membrane
Transmits a signal
e.g generation of cAMP by adenylyl cyclase
40% of modern drugs target
G protein coupled receptors
Signalling inside the cell: Enzyme coupled receptors
Transmembrane proteins, either an enzyme or directly bound to it (dimerises or form complexes)
Most common are Receptor Tyrosine Kinases
Autophosphorylation causes docking sites for downstream receptors
When Receptor Tyrosine Kinases bind a signalling molecule they form
Dimers in the membrane
Activates phosphorylation domains in the cytosol
Beginning of signal transduction cascade
