Cell to Cell Transduction

Cell to cell signalling
Chemical signalling
Hormones – secreted by specialized cells into the bloodstream. Regulates the activity of distally related tissue
Local mediators – released into the extracellular fluid. Produce response in the cells in the same area
Neurotransmitters – are released by nerves at nerve terminals. Transfer of information between adjacent cells.

Hormones
Receptors for Chemical signals
Ligand – any small molecule that binds to a receptor site. If activates the receptor –agonist, if does not –antagonist, if stimulates the receptor, but unable to elicit maximum response – partial agonist
Receptor – molecule that recognize specifically a ligand. In the unbound state receptor is functionally silent
Acceptor molecules – operate normally in the absence of the ligand. Activity is modified by the ligand

Specificity of response
Cell must poses a specific receptor protein for a specific ligand to be able to respond to it. If ligand is hydrophobic – receptor must be present on the outside of cell membrane. If ligand is hydrophilic -the receptor might be intracellular.
Receptors are classified according to a specific signalling molecule (agonist) that they recognize. Subclassification is made on a basis of the ability to be selectively activated by a specific agonist molecules. Example: acetylcholine receptors, subclass – muscarinic and nicotinic receptors.
Properties of Receptor binding sites
Binding is specific
The specificity of binding is governed by the shape of the binding cleft in the receptor
The specificity of binding confers specificity to the regulation of processes in which receptor is involved.
Binding is reversible
Binding induces a conformational change and a change in the activity of the receptor molecule
No chemical modification of the ligand at the binding site
signal transduction.
receptor types
Membrane-bound receptors with integral ion channels
Membrane-bound receptors with integral enzyme activity
Membrane-bound receptors that couple to effectors through transducing proteins

Intracellular receptors
Ligand-gated ion channels
Agonist binding to a ligand-gated ion channels results in a change in conformation and opening of a gated channels which permits a flow of ions down an electrochemical gradient. Can be intracellular. Example : IP3 (second messenger) interaction with receptor on membrane of endoplasmic reticulum results in opening Ca2+ channels joined with it and Ca2+ leaving the ER
Ligand-gated ion channels
Membrane bound receptors with integral enzyme activity
Ligand binding causes a conformational changes that activates an intrinsic enzyme activity contained within a cytoplasmic domain of the receptor. Signal been transduces via second messenger molecule or modification of activities of intracellular proteins by direct phosphorylation or dephosphorylation
Example – Tyrosine-Kinase linked receptor. Receptor autophosphorilates in response to ligand binding. Effector enzymes (activity of which needs to be modified by ligand-receptor binding) interact with phosphorylated receptor directly or indirectly via transducing proteins
Tyrosine-Kinase linked receptor
Tyrosine-Kinase linked receptor
Membrane-bound receptors with no integral enzyme or channel activity

Seven transmembrane domain receptors couple to effector molecules via a transducing molecule GTP binding regulatory protein (G-protein). Effectors might be enzymes or ion channels.
G-protein linked receptors
Intracellular receptors
Hydrophobic ligands penetrate plasma membrane and bind to receptors within cytoplasm or nucleus
Receptor binds to DNA to regulate gene expression
Takes time to take affect

Steroid hormones: testosterone, oestrogen, cortisol
T4,T3

Intracellular receptors
Transducing proteins
Transduce the signal from seven transmembrane domain (G-protein coupled) receptor to a variety of effector molecules
Three subunits of G-proteins: alpha (bound to GDP), beta, and gamma subunits
Ligand binding causes 1) release of GDP from alpha subunit and 2) attachment of GTP to it’s place. Alpha, beta and gamma complex 3) dissociate from the receptor site and go to 4) activate or inhibit specific effector molecules.
Once the GTP is hydrolysed to GDP by alpha subunit the 5) complex inactivates and returns to the receptor site
G-protein linked receptors