Types of receptor

Types of receptor

1. Types of receptors

2. Ligand-gated ion channels (Inotropic receptors) G - Protein coupled receptor (Metabotropic receptors) Enzymatic receptors (Tyrosine Kinase Receptor) Nuclear Receptor (Transcription factors/ Steroid )

3. General Receptor Mechanism

4. Ionotropic Receptors

5. LIGAND GATED ION CHANNELS Ionotropic Receptors Typically receptors on which neurotransmitters act Timescale: Milliseconds Localization: Membrane Effector: Ion Channel Coupling: Direct Examples: Nicotinic Ach Receptor, GABA A Receptor, Glutamate Receptor, Glycine receptor, 5 Hydroxytryptamine type 3 (5 – HT3)

6. MOLECULAR STRUCTURE Nicotinic Ach receptor studied in great detail Pentameric Assembly of 4 types of subunits α, β, γ and δ 4 membrane spanning α- helices inserted into membrane 2 Ach binding sites, both must bind Ach molecules for receptor activation Lining of central transmembrane pore formed by helical segments of each subunit (negatively charged AA). 5 helices sharply kinked inwards halfway, forming a constriction

7. (Watch video on site for detailed understanding) Sodium influx channels

8. (Watch video on site for detailed understanding) Chloride influx channels

9. GPCR G-Protein Coupled Receptors

10. Metabotropic or 7 – Transmembrane/ Heptahelical receptors Largest family Timescale: Seconds Location: Membrane Effector: Channel or Enzyme Coupling: G- Protein Examples: adrenoceptors, Muscarinic Ach, histamine, serotonin, opioid, cannabinoid, amine, peptide, prostanoid receptors TYPE 2 : G – PROTEIN – COUPLED RECEPTORS

11. Single polypeptide chain 1100 residues. 7 Transmembrane α- helices, an extracellular N-terminal domain and intracellular C-terminal domain 3rd cytoplasmic loop couples to the G- Protein MOLECULAR STRUCTURE

12. Family of membrane-resident proteins whose function is to recognize activated GPCRs and pass on the message to the effector systems that generate a cellular response Function of G-Protein: 3 subunits (α, β, γ) are anchored to the membrane through attached lipid residues Coupling of the α subunit to an agonist-occupied receptor causes bound GDP to exchange with intracellular GTP; α–GTP complex dissociates from receptor and from βγ complex Four main classes of G-protein (Gs, Gi, Go and Gq) show selectivity with respect to both the receptors and the effectors with which they couple G-PROTEINS AND THEIR ROLE

13. (Watch video on site for detailed understanding)

14. (Watch video on site for detailed understanding) Gi signalling pathway

15. Gq signalling pathway

16. (Watch video on site for detailed understanding) G signalling pathway

17. Kinase Linked Receptors (RTK) (Receptor Tyrosine Kinase)

18. Location: Plasma membrane Function: Enzymatic activity Function of any Kinase enzyme: catalysis of phosphate group transfer Kinase in this receptors transfers phosphate from ATP to amino acid tyrosine. Inactive as monomers: Active as dimers (when phosphorylated) Examples: Growth factors, cytokines, insulin, etc. Characteristics of Tyrosine kinase receptors

19. Activation of RTK

20. When RTK are phosphorylated they gets activated and further activates various proteins for cellular response. Two Pathways are generally followed by activation of RTKs A. JAK-STAT Pathway B. Ras- Raf MAP Kinase Pathway This pathways initiates gene expression and protein synthesis Intracellular signalling after activation

21. JAK – Janus Kinase STAT – Signal transducer and activator of transcription GRB2 protein – Growth factor receptor bound protein Sos protein – son of sevenless MAP Kinase – Mitogen activated protein kinase ERK – Extracellular signal regulated kinases Important Terms

22. JAK – STAT PATHWAY

23. RAS RAF MAPKINASE PATHWAY

24. (Watch video on site for detailed understanding)

25. (Watch video on site for detailed understanding)

26. (Watch video on site for detailed understanding)

27. Nuclear Receptors (Intracellular Receptors)

28. Location: Cytoplasm and nuclear Function: Intrinsic transcription factor activity Structure: Simple protein structure with two ends (one with N terminal and other with C terminal) DNA binding domain contains zinc finger motif, which is specifically required to bind with DNA. HSP is heat shock protein and it plays important role Examples: Steroid receptors, Vitamin D, PPAR-gamma, Retinoic acid receptor, etc. Characteristics of nuclear receptors

29. Structure of Nuclear Receptors Hinge region

30. Two types of receptors: A. Cytoplasmic B. Nuclear Intracellular signalling after activation Cytoplasmic Receptors Nuclear Receptors Homodimer required Heterodimer required Binds DNA after activation Already bound to DNA When inactive, bound to HSP90 and after ligand binding, HSP90 detach In inactive stage, bound to repressor and detach when activated Eg: Steroids (GC, Estrogen, androgen) , Vitamin - D Eg: Retinoic acid, PPAR gamma, Thyroid receptor

31. Cytoplasmic Receptor (Watch video on site for detailed understanding)

32. Nuclear Receptor (Watch video on site for detailed understanding)

33. Thank You