Cell Signalling Flashcards
What are examples of Endocrine Communication?
( Hormone travels within blood to act on distant target cell )
Insulin produced in pancreas acting on liver, muscle, adipose tissue
Adrenaline produced in Adrenal glands acting on trachea
What are examples of Paracrine Communication?
( Hormone acts on an adjacent cell )
Nitric oxide produced by endothelial cells in blood vessels
Osteoclast activating factors produced by adjacent osteoblasts
How does Insulin have both endocrine and paracrine effects?
Endocrine : Effects on liver
Paracrine : Secreted from beta cells and inhibits release of glucagon from adjacent alpha cells
What is an example of signalling between proteins attached to membranes?
Blood borne viruses are detected by antigens on APCs
They then digest pathogen to express a MHC with class II molecules on surface
T lymphocytes engage through their own TCR interaction
What detects HIV GP120 glycoproteins?
CD4 receptors on T lymphocytes ( Membrane attached protein signalling )
What is Autocrine signalling? What are some examples of it?
Signalling molecule acts on the same cell.
Acetylcholine on presynaptic M2- muscaranic receptors
Activated T cell releases IL-2 and expresses an IL-2 receptor
During Neurotransmission, when is cell signalling used?
Propagration of action potential by depolarisation and repolarisation
NT released from vesicles
Activation of post synaptic receptors
How do Ionotropic receptors work?
Ligand binds to receptor protein
Channel protein changes shape = pore
Ions move along gradient
What is the structure of a G-coupled receptor?
The channel protein crosses cell membrane 7 times
Linked to intracellular G protein complex :
alpha subunit ( are separated into 3 categories )
beta-gamma subunit
GDP molecule
How do Enzyme linked receptors work?
Ligand binding causes receptors to cluster
Clustering activates enzyme activity within cytoplasmic domain
Enzymes phosphorylate receptor
This causes signalling proteins to bind to cytoplasmic domain
Signalling recruits further signalling
What are Intracellular receptors?
A membrane permeable ligand binds to receptors inside cells
What type of receptor does the ligand ACh use?
Ionotropic receptor
Nicotinic Acetylcholine
In skeletal muscles
Causes muscle contraction
What receptors are used for
GABA
Glutamate
5-HT
( Ionotropic )
GABA(A) - inhibition of neuronal activity
NMDA - synaptic plasticity and memory formation
5-HT(3) - anxiety, emesis
Which three categories are G-alpha subunits separated in and what are their roles?
G-alpha q/11 - ( 2nd messenger) Activates PLC ( effect 1) PIP(2) hydrolysed into IP(3) and DAG ( effect 2 ) Ip(3) promoted Ca2+ release from intracellular stores . DAG activates non-selective ion channels
G-alpha s - ( 2nd messenger ) Activates AC ( effect 1 ) Converts ATP to cAMP ( effect 2 ) Activates PKA
G-alpha 1/o - ( 2nd messenger ) Inhibits AC ( effect 1 ) Reduces cAMP formation ( effect 2 ) inhibits PKA
How are 7-TM receptor and heterotrimeric G-protein made active?
They are inactive
Ligand binding changes shape of receptor
Unassociated G-protein binds to receptor
Bound GDP molecule phosphorylated to GTP
G protein dissociated into an alpha and beta-gamma subunit
The subunits bind to their target proteins
How are the 7-TM receptor and heterotrimeric G-protein made inactive?
GTPase in cell acts on alpha subunit which desphorylates the GTP into GDP
beta-gamma subunit also leaves target protein and both join to make the inactive G protein
- If 7-TM receptor is active because ligand remains bound, further heterotrimeric G proteins can be activated
What do G-alpha and G-beta-gamma subunits act as?
Secondary Messengers
Give Examples of G protein-coupled receptors with their respective ligands and physiological effects? (4)
Angiotensin II –> AT-1 receptor. G-alpha q subunit :
Vasoconstriction, increased blood pressure
Acetylcholine –> M3 muscarinic receptor. G-alpha q subunit : Bronchoconstriction, decreased air flow
NE/ Ad –> Beta1 adrenergic receptor. G-alpha s subunit :
Increased heart rate, increased force on contraction
Dopamine –> D1 receptor. G-alpha s subunit :
Increased neuronal growth
Which Enzyme linked receptors do:
Insulin
ANP/BNP
TGF beta
Bind to?
Insulin CD220 receptor. Enzyme : Tyrosine kinase
NPR1 receptor. Enzyme : GC ( vasodilation, reduces bp )
TGF beta R1. Enzyme : Ser/Thr Kinase ( apoptosis )
What do Steroid Hormones target?
They are hydrophobic so go directly to intracellular receptors.
Mostly transcription factors
What are Type I intracellular receptors?
In cytosol
Receptors are bound to chaperone molecules
When hormone binds the chaperone molecule dissociates
The hormone-receptor complex joins another hormone-receptor complex to form a homodimer
Homodimer goes to nucleus to bind to DNA ( acts as transcription factor )
What are Type II intracellular receptors?
In nucleus ( often already bound to DNA )
Hormone ligand binding leads to directly transcriptional regulation as Hormone-complex is activated straight away
How does the hormone Cortisol cause stress, immunosuppression and gluconeogenesis?
Binds to GC-R in cytosol. ( Type I intracellular receptor )
Regulates transcription
How does Estradiol result in female sexual development?
Binds to Cytosolic ER-alpha receptor. ( Type I intracellular receptor )
Regulates transcription
How does Thyroxine cause increased metabolism and greater physical development?
Binds to nuclear TR-alpha receptor. ( Type II intracellular receptor )
Regulates transcription
Which condition is due to a disorder of membrane-attached proteins
lupus
multiple sclerosis
Myasthenia gravis
rhuematoid arthiritis ?
(which one?)
Which receptor class: ErbB receptor
Enzyme linked ( I think )
