INTERCELLULAR COMMUNICATION AND SIGNAL TRANSDUCTION

1. INTERCELLULARCOMMUNICATION AND SIGNAL TRANSDUCTION DR. ZAHOOR ALI SHAIKH LECTURE--- 4

2. INTERCELLULAR COMMUNICATION • HOW CELLS COMMUNICATE WITH ONE ANOTHER ? • Intercellular communication can take place either directly or indirectly. • The most common means of communication between the cells is indirect. • We will study both.

3. INTERCELLULAR COMMUNICATION • Intercellular Communication: 1) Direct 2) Indirect • Direct Intercellular Communication It involves physical contact between the cells.

4. INTERCELLULAR COMMUNICATION DIRECT • Methods of Direct Communication i) Through Gap Junctions ii) Through Surface Markers • i) GAP JUNCTIONS In some tissues minute tunnel or gap are present between the neighboring cells. Through gap junctions, small ions and molecules are exchanged between the cells, without ever entering the extracellular fluid. Gap junctions are present in cardiac muscle.

5. INTERCELLULAR COMMUNICATION DIRECT • ii) Through Surface Markers Some cells like those of immune system, have specialized markers on the surface of membrane that can recognize body own cells and selectively destroy only undesirable cells e.g. cancer cells.

7. INTERCELLULAR COMMUNICATION INDIRECT • Indirect Communication Between Cells • Most cells communicate Indirectly through Extracellular Chemical Messengers or Signal molecules. • There are FOUR types of indirect communication 1) Paracrines 2) Neurotransmitters 3) Hormones 4) Neurohormones

8. INTERCELLULAR COMMUNICATION INDIRECT • 1. Paracrine • These are local chemical messengers, therefore its effect is on only near by cells. Effect occurs due to diffusion of chemical messenger within interstitial fluid. • Chemical messenger does not go into the blood in significant quantity as it is destroyed by local enzymes.

9. INTERCELLULAR COMMUNICATION INDIRECT • Paracrine • Example of Paracrine Indirect Communication: Release of Histamine by connective tissue cell during tissue injury. Histamine causes local vasodilatation to increase blood flow.

10. Paracrine Secretion • Local chemical messengers • Exert effect only on neighboring cells in immediate environment of secretion site

11. INTERCELLULAR COMMUNICATION INDIRECT • 2. Neurotransmitter Nerve communicate with the cells, they innervate by releasing Neurotransmitters. Neurotransmitter diffuses through narrow extracellular space (cleft) to act locally on target i.e. another neuron, muscle, or gland.

12. Neurotransmitter Secretion • Short-range chemical messengers • Diffuse across narrow space to act locally on adjoining target cell (another neuron, a muscle, or a gland)

13. INTERCELLULAR COMMUNICATION INDIRECT • 3. Hormones Hormone are long range chemicals messengers, secreted into blood by Endocrine glands. They effect on target cells, some distance away from their site of release.

14. Hormonal Secretion • Long-range messengers • Secreted into blood by endocrine glands in response to appropriate signal • Exert effect on target cells some distance away from release site

15. INTERCELLULAR COMMUNICATION INDIRECT • 4. Neurohormones • Hormones released into blood by Neurosecretory neuron. • E.g.– Vasopressin is the hormone produced by nerve cells in the Brain. It goes in the blood and acts on the kidney to cause increased water reabsorption.

16. Neurohormone Secretion • Hormones released into blood by neurosecretory neurons • Distributed through blood to distant target cells

17. SIGNAL TRANSDUCTION • Signal Transduction refers to a process by which incoming signals (instructions) coming to the target cell, are transformed into required cellular response.

18. How Signal Transduction Occurs? • It depends on messenger and receptor . Response occurs by three ways: 1. By opening or closing chemically gated receptor channels e.g. Na+, K+ 2. By activating receptor – enzyme e.g. protein kinases 3. By activating second messenger via G-Protein

19. 1. By Opening & Closing Chemically Gated Receptor-Channel

20. 2. By Activating Receptor Enzyme

21. 3. G-Protein Coupled Receptor

25. Activating Through G-Protein • Most extra cellular chemical messengers activate second messenger pathway via G-Protein – coupled receptors. [a]. When first messenger, which is chemical messenger brings signal to the receptor. [b]. Binding of first messenger to the receptor activates G-Protein.

26. Activating Through G-Protein [c]. G-Protein acts via second messenger - Cyclic Adenosine Mono Phosphate [cAMP] - or It may be Ca2+. And causes required bio-chemical reactions in the cell • NOTE – About half of all the drugs used, act via G-Protein coupled receptors e.g. drugs used for blood pressure, asthma, pain.

27. Second Messenger Cyclic AMP • How cAMP works ? • First messenger acts on receptors on the cell membrane and activates G-Protein. G-Protein activates Adenylyl Cyclase enzyme. • Adenylyl Cyclase induces conversion of ATP to cAMP by clearing off two phosphates.

28. Second Messenger Cyclic AMP • cAMP acts as intracellular second messenger. cAMP activates specific intracellular enzyme, protein kinase A. • Protein kinase A activates protein enzymes which bring the desired response.

29. Ca2+ SECOND MESSENGER PATH WAY • Some cells use Ca2+ as Second Messenger instead of cAMP. • In this case, first messenger causes G-Protein to activate the enzyme phospholipase C. • Ca2+ stored in endoplasmic reticulum is mobilized – Ca2+ acts as Second Messenger. • Ca2+ activates calmodulin [Ca2+ binding protein]. • Calmodulin activates required proteins to bring the final response.

30. REMEMBER • Second Messengers are 1. Cyclic AMP [cAMP] 2. Ca2+

33. WHAT YOU SHOULD KNOW FROM THIS LECTURE? • What in intercellular communication? • Types of intercellular communication - Direct – through gap junction - through surface markers - Indirect – paracrine, - neurotransmitters - hormones - Neurohormones • Signal transduction - By opening or closing chemically gated receptor channel - By activating receptor enzymes - By activating second messenger by G protein coupled receptors

34. THANK YOU