4 reasons for cell signalling?
- To process information
- For self preservation
- For voluntary movement
- For homeostasis
4 steps to neurotransmission?
- Propagation of action potential (AP) in pre-synaptic neurone- Na+ influx and K+ outflux to depolarise membrane
- Neurotransmitter (NT) release from vesicles- AP opens voltage-gated Ca2+ channels at presynaptic terminal which causes vesicle exocytosis
- Activation of postsynaptic receptors- NT binds to receptors on post-synaptic membrane and receptors modulate post-synaptic activity
- Signal can be transmitted by a variety of different types of receptor
Endocrine communication and example
Hormone acts on a distant target cell. E.g glucago targeting liver cells
Paracrine communication and example
Hormone acts on adjacent cells. E.g insluin inhibiting glucagon secretion
Membrane receptor communication and example
APC presenting MHC class II molecules on surface and binding to circulating T-lymphocyte
Autocrine communication and example
Signalling when molecule acts on same cell. E.g T-cell secreting IL-2 to bind to IL-2 receptors on itself
Chemical messages or molecules?
Ligands
Ligand-gated ion channel receptors (ionotropic receptors)?
- Ligand binds to receptor protein
- Conformation change of channel protein opens pore in membrane
- Ions move in or out of the cell according to concentration gradient
G protein-coupled receptors?
- At rest, the G protein complex consists of a Ga subunit, a GBy subunit and an associated GDP molecule close to the receptor
- Ligand binding causes the complex to associate with the receptor resulting in the GDP molecule being phosphorylated to a GTP molecule
- Ga subunit dissociates from the Gby subunit
- Ga and Gby act as second messengers
- When the ligand dissociates from the receptor, internal GTPase on the Ga subunit hydrolyses GTP to GDP
- Ga and Gby subunits re-associate and are once again available to the receptor
Enzyme-linked receptors?
- Ligand binding results in receptors clustering
- Enzyme activity activated in cytoplasmic domain
- Enzymes phosphorylate receptor
- Phosphorylation leads to binding of signalling proteins to the cytoplasmic domain
- Other signalling proteins recruited and signal in cell generated
- Signal terminated when a phosphatase dephosphorylates the receptor
Intracellular Receptors?
Essentially transcription factors controlled by membrane permeable steroid hormones
Two types of intracellular receptors?
- Type I: located in cytosol. Hormone binds to receptor, hsp dissociates so complex can form a homodimer and translocate to the nucleus
- Type 2: located in nucleus and are often bound to DNA. Binding of hormone ligand results in direct transcriptional regulation by activated complex
Example of ligand-gated receptor?
GABAa
Example of G protein-coupled receptor?
B1 adrenergic
Example of enzyme-linked receptor?
NPR1
Example of intracellular receptor
TRa
