Receptors abd its type

1. RECEPTOR AND SIGNAL
TRANSDUCTION MECHANISMS
Group D (Roll no : 51-66)
First semester students
Nepalgunj medical college, Basic scienc
Chisapani , Banke.

2.  Definition : Receptors are proteins which
binds with the hormones, neurotransmitter
and other chemical substance with the great
affinity and specificity to produce cellular
response.
Function of receptors
 To propagates regulatory signals from outside to inside the effector
cells
 To amplify the signal.
 To integrate various extracellular and intracellular regulatory signals.
 To adapt to short and long terms changes in the regulatory milieu and
maintain homeostasis

3. SIGNAL TRANSDUCTION MECHANISM
 Highly complex Multistep process that helps in amplification
of signal
 Integration of concurrently received extra and intracellular
signal of each step.
Transducer mechanism can be grouped into 5 major categories
1. Ion channel linked receptor
2. G protein coupled receptor
3. Enzyme linked receptor
4. JAK STAT binding receptor
5. Nuclear Receptor

4. 1. Ion Channel linked receptors
These receptors are localised on cell membrane and are coupled
directly to an ion channel.
These “agonist regulated ion channels “ (also known as ligandgated
ion channels) open only when the receptor is occupied by an agonist.
Are also called the “ Receptor Operated Channels ( ROCs)”.
ROC is distinct and different than “Voltage Operated (or gated) ion
channel(VOC).
Examples include: nicotinic-cholinergic, GABAA receptor; glutamate
receptor and the glycine receptor.

6. Binding of Acetylcholine to nicotinic receptors.
It will cause opening of ligand gated Na+ channel.
↑Permeability of Na + and K +
Large no of Na + ions enter the muscle fiber and few K + move
out ↓in negativity of membrane from -90 mv- 60 mv
Genesis of End plate potential and When end plate potential
reached threshold opening of voltage gated Na ion channels
Generation of action potential and Contraction of muscle

7. 2. Metabotropic receptor
(G-protein coupled receptor )
 All G protein coupled receptor transverse the cell membrane
seven times hence they are also called seven helix receptor or
serpentine receptor.
 There are 16 α subunits, 5 β subunits and 11 γ subunits.
 These α, β, and γ subunits can assemble into hundreds of
different combinations and thereby interact with a diverse
number of receptors and effectors

8.  In the absence of ligand, G protein
are inactive and form heterotrimeric
complexes in which GDP bind to
alpha subunit.
When ligand bind to receptor, the
activated receptor induces
conformational changes that promote
release of GDP and binding of GTP to
alpha subunit.
.

10. There are two major effector pathways through
which GPCRs function.
1. Phospholipase C: IP3-DAG pathway
2. Adenylyl cyclase: cAMP pathway

12.  Binding of GTP to alpha subunit causes dissociation
of alpha subunit from BY dimer.
 Alpha subunit with GTP may activate adenylyl
cyclase, Phosphodiesterase and
Phospholipase.(signalling molecule)
 This causes further downstream signalling leading
to cell response.

14. 3. Catalytic receptor or Enzyme linked receptor
They are known as one pass receptors.
Receptor guanyl cyclases: ANP and nitric oxide
Receptor tyrosine kinase: Insulin, epidermal growth
factor

15. Transmembrane Enzyme linked Receptor
 Recognised as Receptor Tyrosine kinase (RTK)
 Eg: Epidermal growth factor, PDGF and Insulin
 Insulin receptor are tetrameric composed of 2 α and 2β subunits.
 α subunit is present extracellularly but β subunit is present
intracellularly.

16. Peptide hormone bind to α subunit which is present extracellularly
conformational change which facilates interaction between 2 α and 2β pairs.
activation of Tyrosine protein Kinase activity in intracellular domain and
autophosphorylation of Tyrosine residues in catalytic domain of β subunit.
Phosphorylates cytoplasmic protein to initiate its cellular effect.
Perform downstream signalling

18. 4. Transmembrane JAK-STAT binding
receptors
 These receptors differ from RTKs in not having any intrinsic catalytic
domain.
 Agonist-induced dimerization alters the intracellular domain
conformation to increase its affinity for a cytosolic tyrosine protein
kinase JAK (Janus Kinase).
 On binding, JAK gets activated and phosphorylates tyrosine
residues of the receptor, which now bind another free moving
protein STAT (signal transducer and activator of transcription).
 Pairs of phosphorylated STAT dimerize and translocate to the
nucleus to regulate gene transcription resulting in a biological
response.

19. Many cytokines, growth hormone, prolactin, interferons, etc. act
through this type of receptor.
There are four JAKs and six STATs in mammals which, depending on
the cell type and signal, combine differently to activate gene
transcription.
For example, prolactin appears to use JAK1, JAK2, and STAT5 to
stimulate milk production.

21. The intracellular domain of these receptors lacks intrinsic protein kinase activity.
Cytokines/hormones binding to the extracellular domain induce receptor dimerization which
activates the intracellular domain to bind free moving JAK (Janus Kinase) molecules.
The activated JAK phosphory- late tyrosine residues on the receptor which then binds another
protein STAT (signal transducer and activator of transcription).
Tyrosine residues of STAT also get phos- phorylated by JAK. The phosphorylated STAT
dimerize, dissociate from the receptor and move to the nucleus to regulate transcription of
target genes.

22. 5. Nuclear Receptor
Also know as Cytosolic receptor or intracellular receptor.
Binding site for steroid hormone.
Slowest acting receptor Present in the cytoplasm
Glucocorticoids, mineralocorticoids, and vit. D or in the nucleus
(T3, T4, Retinoic acid, estrogen, progesterone and testosterone).
This type of receptors finally act by nuclear mechanisms (i.e. by
affecting transcription).

23. Steroids
bind to receptors in cytoplasm
steroid-receptor complex
migrates to nucleus
binds to specific site on the DNA
regulate protein synthesis
response

24. “Medicines are nothing in themselves but are the very hands of
God if employed with reason & prudence.”
-The Alexandrian physician Herophilus-300 B.C.
THANK YOU !!!

25. Special Thanks to
 Dr. Aswani Chaudhary
 Ms. Ankita Singh
 Dr. Ritesh Singh
 Dr. Vikash verma