cell signalling 2

What are the 4 main classifications of receptors?

• G-protein coupled receptors (membrane bound)

• Intrinsic enzyme receptors (membrane bound)

• Ion Channel receptors (membrane bound)

• DNA Binding receptors (in cytoplasm but once activated moves to membrane)

What is the cellular location of the receptors

• Nuclear receptors are present in the nucleus

• Intracellular receptors are present on the endoplasmic reticulum

• Plasma membrane receptors are present on the membrane

what recptors are found at plasma membrane

• G-protein coupled receptors

• Tyrosine kinase receptors

• Ligand-gated ion channels

what receptors are found at the Nuclear receptors

DNA binding receptors

what are intrinsic enzyme receptors and give an example of one

• recpetor that has one part that the ligand binds to and another that has an enzyme that becomes activated when the ligand binds 

• they are receptors for growth hormones, cytokines,insulin

• e.g  Tyrosine Kinase Receptors (RTKs),insulin

explain what are tyrosine kinase receptors (RTK) and how they work

• a type of intrisic enzyem recpetor

• it has a ligand binding site outside of the membrane the transmemebrane section and an enzyme inside the cell

• before a ligand binds the RTK are monomers ( by itself) 

• when the ligand binds it makes 2 recpetors come together this is dimersation 

• wehn they dimerase the internal enzyme activate and do autophosphorylation -  phosphorilate eachother 

• this is now the binding site for other signalling proteins making a cascade of reactions

RAS-MAP Kinase siganlling pathway

- how to controll cell growth division and differnetiation

1. Ligand binds to receptor on RTK

2.  autophosphorylation of RTK makes the internal enzyme actiavte

3. Recruitment of RAS (monomeric G protein)

4. Exchange of GDP for GTP on RAS results in it becoming avtivated (startign the cascade reaction) 

5. this activates the MAP kinase kinase kinase 

6. This activates MAP kinase kinase

7.  This activates MAP kinase

   1. These 3 steps are a series of phosphorylation events

   2. So there is an exchange of phosphate from ATP to the protein causing conformational change that activates the enzyme

8. This cascade can cause two effects

   1. Cause transcription within the cell  changing gene expression

   2. Phosphorylates 2 different proteins within the cell to produce 2 different signalling cascades

describe the structure and function of insulin receptors

• they are dimers ( made of 2 monomers jpined by disulfide bonds)

• made of 2 alpha and 2 beta subunits each monomer made of one alpha one beta subunit

• when a ligand bind it makes conformation change instead of makign a dimer

• the effect is it makes a signalling cascade all to decrease blood glucose concentration: making more glucogen, increasing uptake fo glucose, increase use of glucose, dercease formation of gluose

what is the revelance of RTK signalling to dentistry

1.  Craniofacial & Tooth Development

2.  Periodontal & Bone Regeneration

3. Salivary Gland Function & Disorders

4.  Oral Cancer & Pathology

what are other names for ion channel recpetors

• Ionotropic receptor

•  Receptor operated ion channel

how are ion channels clasified and what are the 4 types

Can be classified by the type of stimulus that opens these channels

⚬ Ligand-gated 

⚬ Voltage-gated 

⚬ Temperature-sensitive ion channels 

⚬ Mechano-sensitive ion channels 

can also be clasified by the ion they let pass through

in genral how do ion channel receptors work

• using the differnce in concentration of an ion inside/outside of a cell 

what is an ionotropic ion channel and what are the 3 main types

• proteins that open a pore in the membrane and when a ligand binds it allows specific ions to pass

• pentameric 

• tetrameric

• trimeric

explain pentameric ion channels

• a type of ionotropic ion channel 

• Made of 5 proteins forming a central pore that the ions travel through

• anion examples and its receptor: Na+, Ca2+,K+ → Nicotinic acetylcholine (nACh) receptors , Serotonin type 3 (5-HT3) receptors

• cation examples and its receptor: Cl- →  Glycine (Gly) receptors, GABA-A receptors

explain Trimeric ion channels

• Made of 3 monomers forming the pore.

• they are ATP actiavted ion channels e.g P2X receptors 

• only let anions through 

• Ions: Na⁺, K⁺, Ca²⁺ → depolarise cell → excitatory → generate EPSPs

• help with Synaptic transmission, pain perception, inflammation,

  and the contraction of smooth muscles

explain Tetrameric ion channels

• Made of 4 monomers forming the pore.

• Hydrophobic amino acids line the inside of each monomer.

• its a volatge gated ion channel 

• only let anions, Ionotropic glutamate receptors

• Ions: Na⁺, K⁺, sometimes Ca²⁺ → depolarise cell → excitatory

• example of receptor: Ionotropic glutamate receptors ,NMDA receptors, AMPA receptors

what is the Mechanism of action of ligand-gated ion channels (LGIC)

• Inactive (closed) until a ligand binds to the receptor.

• Ligand binding opens the pore making a conformational change in shape that moves the  hydrophobic residues from the central part of the pore and lettign hydrophilic residues ine it instead 

• Ions are hydrophilic, so they must pass through the channel, not the lipid membrane.

• Cation entry 

how does acetyl choline receptor work

1. Closed conformation, hydrophobic amino acid side chains at gate keep pore closed so the channel is hydrophobic and the ions which are hydrophilic cannot enter the receptor

2. Acetylcholine binds to receptor conformational change

3. Takes the hydrophobic amino acids away from the pore and allows hydrophillic amino acids to fill the pore

4. This allows the gate to opens and ions enter cell (open conformation)

5. allows Na+ to enter and bind to the post synpatic cell

6.  chaning the membrane potential letting the elctriccal signal continue 

7. Cell signalling cascade can occur

explain how a excitatory synpase works

Neurotransmitter binds → Na⁺ enters → depolarisation → inside becomes less negative → increases likelihood of firing an action potential if threshold met.

explain how inhibitory synapses work

Neurotransmitter binds → Cl⁻-  enters → hyperpolarisation → inside becomes more negative → decreases likelihood of firing an action potentialas theshold wont be met. 

what are DNA receptors

• Also called: nuclear receptors

• Location: inside the cell (intracellular)

• Function: act as ligand-activated transcription factors → regulate gene expression

• Ligands: lipophilic hormones that can cross the membrane:

Steroid hormones
Thyroid hormones
Vitamin D
Retinoic acid

• there are 2 main types of DNA binding recpetors: 

1. Type I – Cytoplasmic receptors

2. Type II – Nuclear receptors already in the nucleus

Mechanism of action of type I DNA binding receptors

• in the cytoplasm of the cell 

• Usually bound to inhibitory proteins (heat-shock proteins) in the cytoplasm.

• Ligand binds 

• receptor releases inhibitory proteins 

•  the recpetor dimerises 

• dimer moves to nucleus 

•  binds DNA making activatign trasncription

• e.g of receptors are  Androgen receptor, Estrogen receptor, Glucocorticoid

•  

Mechanism of action of type II DNA binding receptors

• already in nucleas and bound to DNA unliek type 1 

• Ligand binding to receptor 

•  changes conformation

•  activates proteins that start transcription.

• Examples: Thyroid hormone, Retinoic acid receptors.

Relevance of DNA binding receptors to dentistry

• Vitamin D Receptor: Controls calcium & phosphate → tooth mineralisation & bone health

• Estrogen Receptors: Affect periodontal tissue remodeling → may influence periodontal disease risk

• Retinoic Acid Receptors: Regulate craniofacial development, tooth/salivary gland morphogenesis, and tooth mineralisation

• Glucocorticoid Receptors: Modulate inflammation → important in oral inflammatory condition management

summary of receptors

Relevance of Cell Receptors to Dentistry

• Drug Targets: ( drugs bind to receptors ) Pain, inflammation, bone remodelling, cancer 

• Precision Medicine: ( receptors are differnt in disease or normal cells) Target diseased cells, reduce side effects, develop biomarkers

• Regeneration & Healing: Control stem cells, angiogenesis, and tissue repair 

explain Thermo-sensitive ion channels in odontoblasts

• here are thermosensitive ion channels in the dentin that when theres change in temperature it can lead to pain

explain Mechano-sensitive ion channels in dental pulp and periodontal ligament

• in pulp there is mechanoreceptors

• they detect pressure on teeth and help initiate bone remodoling adjusting the tooths postion making it more stable 

Relevance of ion channels to dentistry

• Pain: Na⁺ channels transmit signals; blocked by local anaesthetics → pain relief

• Tooth Mineralisation: Ca²⁺ channels regulate enamel/dentin formation; disruption → defects

what are DNA-bidning receptors

proteins that can bind to DNA controling gene trasncription after its been actiavted by a ligand