Receptor Mediated Endocytosis

Receptors are the sensing elements in the system of chemical communications that coordinates the function of all the different cells in the body and receptor is a protein molecule, embedded in either the plasma membrane or the cytoplasm of a cell, to which one or more specific kinds of signaling molecules may attach.
Endocytosis is a cellular process in which substances are brought into the cell
It is of three types
1. PHAGOCYTOSIS
2. PINOCYTOSIS
3. RECEPTOR MEDIATED ENDOCYTOSIS

1. Presented By: T.SATYAVATHI M.PHARMACY II SEMESTER DEPT.OF PHARMACEUTICS RECEPTOR-MEDIATED ENDOCYTOSIS 1

2. CONTENTS Introduction Receptor-Mediated Endocytosis and Exocytosis Ligands that enter by receptor mediated endocytosis Conclusion References 2

3. INTRODUCTION 3 RECEPTORS: Receptors are the sensing elements in the system of chemical communications that coordinates the function of all the different cells in the body. Receptor is a protein molecule, embedded in either the plasma membrane or the cytoplasm of a cell, to which one or more specific kinds of signaling molecules may attach.

4. ABSORPTION 4 The Process of movement of unchanged drug from the site of administration to systemic circulation.

5. Pathogens use the endocytic pathway to get into cells e.g.: flu virus Salmonella ?

6. PHAGOCYTOSIS PINOCYTOSIS ENDOCYTOSIS RECEPTOR MEDIATED ENDOCYTOSIS 6

7. TYPES OF ENDOCYTOSIS 7

8. PHAGOCYTOSIS 8

9. PINOCYTOSIS 9

10. TRANSCYTOSIS 10

11. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Extracellular fluid Intracellular fluid Receptor 1

12. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Clathrin- coated pit Extracellular fluid Intracellular fluid Receptor- ligand migrates to clathrin -coated pit. Clathrin Receptor 1 2

13. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Clathrin- coated pit Extracellular fluid Intracellular fluid Receptor-ligand migrates to clathrin-coated pit. Endocytosis Clathrin Receptor 1 2 3

14. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Clathrin- coated pit Extracellular fluid Intracellular fluid Receptor-ligand migrates to clathrin-coated pit. Endocytosis Vesicle loses clathrin coat. Clathrin Receptor 4 1 2 3 4

15. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Clathrin- coated pit Extracellular fluid Intracellular fluid Receptor-ligand migrates to clathrin-coated pit. Endocytosis Vesicle loses clathrin coat. Clathrin Endosome Receptors and ligands separate. Receptor 4 1 2 3 4 5

16. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Clathrin- coated pit Extracellular fluid Intracellular fluid To lysosome or Golgi complex Receptor-ligand migrates to clathrin-coated pit. Endocytosis Vesicle loses clathrin coat. Ligands go to lysosomes or Golgi for processing. Clathrin Endosome Receptors and ligands separate. Receptor 4 1 2 3 4 6 5

17. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Clathrin- coated pit Extracellular fluid Intracellular fluid To lysosome or Golgi complex Receptor-ligand migrates to clathrin-coated pit. Endocytosis Vesicle loses clathrin coat. Ligands go to lysosomes or Golgi for processing. Transport vesicle with receptors moves to the cell membrane. Clathrin Endosome Receptors and ligands separate. Receptor 4 1 2 3 4 7 6 5

18. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Clathrin- coated pit Extracellular fluid Intracellular fluid To lysosome or Golgi complex Receptor-ligand migrates to clathrin-coated pit. Endocytosis Vesicle loses clathrin coat. Ligands go to lysosomes or Golgi for processing. Transport vesicle with receptors moves to the cell membrane. Transport vesicle and cell membrane fuse (membrane recycling). Clathrin Endosome Receptors and ligands separate. Receptor 4 1 2 3 4 8 7 6 5

19. Receptor-Mediated Endocytosis and Exocytosis Ligand binds to membrane receptor. Clathrin- coated pit Extracellular fluid Intracellular fluid To lysosome or Golgi complex Receptor-ligand migrates to clathrin-coated pit. Endocytosis Vesicle loses clathrin coat. Ligands go to lysosomes or Golgi for processing. Transport vesicle with receptors moves to the cell membrane. Transport vesicle and cell membrane fuse (membrane recycling). Exocytosis Clathrin Endosome Receptors and ligands separate. Receptor 4 1 2 3 4 9 8 7 6 5

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21. Clathrin 21 A coat protein Forms special shape called triskelion 3 heavy chains 1 or 2 light chains associated with each heavy chain Heavy chains are rigid and form a cage type structure Distant side contains the globular domain for binding assembly particles Light chains are attached near the centre Stabilize the structure

22. Clathrin assembly 22 Triskelions assemble into a cage like structure Fibrous network of pentagons and hexagons Can self-assemble and form empty cages

23. Adapter and assembly proteins 23 Assembly is directed by adapter and assembly proteins Adaptins Responsible for specificity of trafficking

24. 24 Dynamin and Vesicle budding Dynamin Globular cytosolic protein GTPase - binds and hydrolyzes GTP Self assembles into a collar Dynamin polymerizes over the neck of the vesicle and pinches the neck off Energy is coming from the hydrolysis of GTP

25. 25 Lysosome The endpoint of the endocytosis pathway for many molecules is the lysosome, a highly acidic organelle rich in degradative enzymes.

26. Types of endocytotic vesicles 26 Use different coats or no coats Have different sizes Have different mechanisms of forming

27. Ligands that enter by receptor mediated endocytosis 27 Nutrients: Cholesterol through LDL receptor Iron with carrier protein transferrin

28. Termination of signalling by receptor mediated endocytosis 28 Hormones and growth factors to terminate signalling: Insulin Catecholamines Prolactin Growth hormone Epidermal growth factor Nerve growth factor

29. Opportunistic Ligands that enter by receptor mediated endocytosis 29 Toxins Diphtheria toxin Pseudomonas toxin Cholera toxin Viruses Rous sarcoma virus Vesicular stomatitis virus Adenovirus

30. Rates of Clathrin mediated endocytosis 30 Class I LDL and transferrin Constitutive (no ligand necessary) Class II Insulin and EGF Active upon ligand binding

31. Rates of Clathrin mediated endocytosis 31 Class III CD4 Tethered to cytoskeletal elements Ligand binding triggers release and endocytosis Class IV Resident plasma membrane pumps Tethered to cytoskeletal elements Internalize slowly if at all

32. CHOLESTEROL UPTAKE 32

33. IRON UPTAKE 33

34. 34 VIRAL ENTRY:

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37. CONCLUSION Receptor-mediated endocytosis is a mechanism used by cells for the internalization of selected plasma-membrane proteins. It is widely used for the specific uptake of certain substances required by the cell such as LDL via the LDL receptor or iron via transferrin receptor etc. The coated pits serve as a mechanism for concentrating the randomly distributed cell surface receptors for efficient internalization of the ligand. An assortment of endocytic vesicles (coated and/or smooth) carry the receptor- ligand complexes into the cells. 37

38. REFERENCES Rang and Dale’s Pharmacology H.P.Rang, M.M.Dale, J.M.Ritter, R.J.Flower.2007:6 th edition:Pg:24-28. D.M.Brahmankar , Sunil B.Jaiswal. Biopharmaceutics and Pharmacokinetics A Treatise. Published by M.K.Jain.1995:1 st edition: Pg:5-8 Principles of Anatomy and Physiology Gerard J.Tortora, Bryan H.DERRICKSON.2006: 11th edition, volume 1:Pg:72-74 Aulton’s Pharmaceutics The Design and Manufacture of Medicines. Edited by Michael E.Aulton.2007:3 rd edition: Pg :283 38

39. REFERENCES 39 Websites : www.utm.utoronto.ca/~w3bio315/RME/examples.html‎ www.uta.edu/biology/wilk/classnotes/cellphys/endocytosis.pdf‎ www-esbs.u-strasbg.fr/ notesdecours /1ere-annee/Cell.../Ch_23.pdf‎ http://en.wikipedia.org/wiki/Receptor-mediated endocytosis

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