cell signalling

Define autocrine signalling.

Signalling back onto the same cell

Define endocrine signalling.

Secretion of hormones into the bloodstream

Define paracrine signalling

Signalling to adjacent cells

What are the three classes of membrane receptors?

• ionotropic: ligand-gated ion channels (e.g. nicotinic acetylcholine receptor)

• metabotropic: 7 transmembrane spanning coupled with G-protein (e.g. glucagon receptor)

• catalytic: linked to tyrosine kinase (e.g. insulin receptor)

What does cAMP do?

• binds to protein kinase A (PKA)

• leads to breakdown of ATP into ADP + Pi

• Pi phosphorylates serine / threonine

• causes a conformational change for short term signalling actions and activating transcription factors (CREB for gene expression)

Where are the 3 locations receptors can be present in?

1) Nuclear receptor in nucleus

2) Intracellular receptor in cytoplasm

3) Plasma membrane receptor in csm

How do intrinsic enzyme receptors (aka receptor tyrosine kinases) work?

intrinsic enzymes are enymes that are part of the receptor inside the cell membreane 

1. a ligand binds to the receptor and i causes dimerising where 2 receptors join together 

2. the receptors autophosphorylate and this actiavtes the receptor and sinalling molecules 

3. this actiavtes RAS which is a g protein outside the membrane,it is actiavted by swicthed GDP for GTP 

4. RAS activates MAP kinase by phsophorylation 

5. map kinase then goes to the nucleas where it can phsophorylate transcription factors changign gene expression 

What is the name of ion channel receptors with 3, 4 and 5 monomers?

Trimeric

Tetrameric

Pentameric

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

what are the 3 different saturations of a fatty acid

1. fully saturated : no double bonds (e.g stearic acid)

2. mono-unsaturated : one double bond ( e.g oleic acid)

3. poly-unsaturated : several double bonds (arachidonic acid)

amphipathic meaning

a molecule has both hydrophilic and hydrophobic regionis

how does the length of the fatty acids chain affect membrane fluidity

short chain less hydrogcarbon chain interaction so increase fluidity

what are lipid rafts

areas that have high cholesterol concentration 

how high cholesterol content affect membrane fluidity

it restricts the movement of polar heads which decreases fluidity 

what 6 things can cell signaling control

1. differentiate 

2. divide

3. store energy

4. die

5. secreet and release

6. grow

what are the 5 steps for communiction by extracellular signals

1. Synthesis and release of the signalling molecule by the signalling cell

2. transport of the signal to the target cell 

3. detection of the sinal by a receptor at the target cell (intercellular or on the membrane)

4. there is a cell response 

5. removal of the signal and terminating the response (only sometimes does the response be terminated)

what are the 4 types of signals

1. hormones and growth factors 

2. metabolic regulators

3. neurotransmitters

4. inflammatory mediators 

endocrine signallign in detail?

1. endocrine glands are stimulated so they synthesis and secrete hormones 

2. the hormones are carried in the blood stream to target cells (can be a few m distance ) 

3. the hormone binds and activates the receptors which stimulate a biological reponse 

paracrine signalling in detail

it is like transmission at a neuromuscular junction 

1. an action potential arrives at the cholinergic nerve terminal 

2. synpatic vesicles release ACh into the synpatic cleft 

3. ACh bind to the ion channles in the muscle cell membrane 

4. Na+ channels open and they eneter the motor fibre

5. this makes a potential

explain how macrophages are an example of autocrine signalling

1. the macrophage release Cytokine Interleukin-1 (IL-1)

2. they also have the receptors for IL-1 

3. when the IL-1 is detected it causes an intercellular casscade for more IL-1 to be made and secreted

4. this is a forward feedback loop whcih maintains the macrophage being inflamed 

what 2 cells have an autocrine signallign system

macrophages- with cytokine interleukin-1 being secreted 

cancer cells- with growth factors beign secreted

what are the 3 stages fro a signal to be converted into a response

1. reception

2. transduction 

3. response

explain signal recption- step 1 of converting a signal to a repsonse

• type 1: most signals are membrane impermiable so bind to cell surface receptor which have

  - high affity

  - highly selective 

• type 2: membrane permiable signals ( steriod hormones) bind to cytosolic receptors ( in cytoplasm) 

what is an ionotropic membrane receptor

- they are ligand gsted ion channels 

-  e.g nicotinic acetylcholine receptor
         ionotrpic glutamate receptors 

what are metabotropic membrane receptors

- 7 transmembrane spanning g-potein coupled
- they are bound to G-proteins 
- they are wrapped around the membrane 7 times 

-e.g glucagon receptor 
- adrenaline receptor 

what are catalytic membrane receptors

- recptors that are directly linked to enzymes inside e.g linked to tryosine kinase 

- e.g insulin receptor 
        nerve groet factor (NGF) recpetor

what are the 2 types of secondary messengers used in transduction

1. second messenger molecules 

2. scaffold proteins and adaptor protein

what happens in the transducer stage

the signal is transmitted to the cytoplasmic side to effector molecules down a signalling pathway 

what are second messenger molecules

• small molecules 

• they relay information from the eteran first messenger into the cell 

• they are 7 transmemberane spannign G protein coupled 

what are scaffold and adaptor proteins

scaffold: proteins with many binding domains 

adaptor: smaller and connect two specific parters 

what do scaffold andd adaptor proteins do

 they bind signalling components together increasing their efficiency and specificity of a signal transductions

- it makes sure the right signallign molecule is in the right place and time to interact 

- tyrosine kinase linked

how are secondary messengers activated

a primary messenger activates an effector enzyme that activates a 2nd messenger 

what 2nd messenger does the effector adenylyl cyclase activate

cyclic AMP ( adenosine 3'-5'-cylcic monophosphate)

what 2nd messenger does the effector phopholipase C activate

IP3 ( inositol 1,4,5-trisphosphate)

1,2-diacylglycerol (DAG)

what is a signalling cascade

when a cell receives a signal a chain of biochemical events take place which amplifies the initial signal 

what is intracellular signalling

when the signalling molecule cannot pass through the membrane so it binds ot the receptors on the surface which leads to a signallign cascade

what are the overall use of secondar,sacffold and adaptor proteins

help to pass signal inside the cell after receptor is activated 

what is an effector enzyme use

to make a signalling cascade you need an effector enzyme to activate/make a secodnary messenger

what is a 7 transmembrane spanning G-protein coupled

• it is a receptor 

• it detects ligands (hormones) at its n terminal, at the membrane so it can make a signalling cascade 

• the n terminal interacts with the ligand the c terminal interacts with the G protein

what does a 7 trasnmembrane spannign g protein receptor look like

what is a g proteins function (simple)

they are molecular switches that move info from the receptor to the effector enzymes

when are g proteins active

when bound to GTP

when are g protein inactive

• active when bound to GTP

• inactive when bound to GDP

what deos it mean that g proteins are heterotrimeric

made of 3 subunits 
alpha 
beta
gamma

what subunit of the g protein is bound to gdp/gtp

alpha

how does the g protein become active

• when gtp binds to the alpha subunit it dissociates

• the free G- a(alpha) ia released 

• this starts the signaling cascade

• to stop it the gtp becomes hydrolysed to gdp and the subunits join together back to 3

  

explain the sequence of steps of GPCR signalling with b androgenic receptors to effector enzymes

1. the hormone ( noradrenaline)  binds to the receptor ( b androgenic receprotr which is a GPCR) on the cell membrane 

2. this changes the shape of the receptor by exposing the intracellular loop 

3. the g protein (which is initialy inactive and bound to GDP ) also bind to the receptor 

4. GTP replaces GDP activating the g protein 

5. the g protein splits into the beta/gamma subuniy and a GTP bound alpha subunit  

6. the alpha moves along the cell membrane findin and activates the effctor enzyme ( e.g adenylyl cyclase )

7. this produces a secondar messenger (e.g atp -cAMP)

8. secondary messenger activates a protein ( e.g PKA )

9. to stop the signalling cascade the GTP is hydrolysed to GDP 

how does cAMP activate protein kinase and what does this do

PKA ( protein kinase A) is made of 4 subunits:
 - 2 regulatory 
 - 2 catalytic 

- cAMP binds to the regulatory subunit of PKA making it change shape and the catakytic subuinits are released 
- the catalytic subunits are used to change ATP-ADP+Pi
- the Pi can be used for short term or long term effects 
- short term: makign a comformation change in shape in enzymes making a repsonse 
- long term: activatign transcriptional factors so geen expression changes

how does the cascade of CAMP be stopped

phosphodiesterase binds to CAMP which form 5'AMP which cant bind to pKA so wont be activated 

what is the fight or flight B adrenergix stimulation

• what is the ligand used

• what are the 2 pathways and thier outcomes

ligand- noradrenaline

1. this activates CAMP

2. CAMP activates PKA

the 2 patwhays are 2 to make more glucose another to decrease the amount of glucose

 

 decrease glucose

1.  PKA inhibits glycogen synthase

2. this decreases glycogen synthesis 

3. this decreases the level of glucose 

4. so less atp made 

increase glucose 

1. glycogen phosphorylase kinase is stimulated 

2. glycogen phosphorylase is stimulated 

3. this increases glycogen degredation 

4. so theres an increase in glucose 

5. so more atp 

what are the differnt G protein, recpetor,effectir,second messenger response

why is g protein relevant in dentistry

1. tissue development 

2. oral tissue 

3. inflammation and immune response 

4. pain and perception and analgesia

5. cancer and oral pathology

explain what is happening

1. befroe the agonist binds to the recerptor the g protein is inactive and cyclase can work 

2. the agaonist binds to the receptor this makes GTP switch with GDP so the g protein dissociates and the aklpha subunit bidns ot cyclase whic inhibits it 

what is an agonist and whata are the 2 types

• molecuel that binds to a recptor activating
  
  natural ligand ( endogenous) 
  
  exogenous (synthetic/drug)

what is a natural ligand and what are examples

• endogenous agonists

• agonisst made in the body 

• e.g epinphrine (adrenaline), 

             norepinephrine (noradrenaline)

what is exogenous agonists

• synthetic agonist

• made outside the body 

• e.g salbutamol