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Receptor Mediated Endocytosis
The document discusses receptor-mediated endocytosis and exocytosis, detailing the role of receptors in cellular communication and the specific mechanisms involved in the uptake of molecules like LDL and iron. It covers various types of endocytosis, including phagocytosis and pinocytosis, and emphasizes the importance of clathrin-coated pits in concentrating surface receptors for efficient internalization. Conclusively, receptor-mediated endocytosis is crucial for cells to selectively internalize necessary substances.
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Receptor Mediated Endocytosis
- 1. Presented By: T.SATYAVATHI M.PHARMACY IISEMESTER DEPT.OF PHARMACEUTICS 1
- 2. CONTENTS Introduction Receptor-Mediated Endocytosis andExocytosis Ligands that enter by receptor mediated endocytosis Conclusion References 2
- 3. INTRODUCTION 3 RECEPTORS: Receptors are thesensing 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 ofmovement of unchanged drug from the site of administration to systemic circulation.
- 5. Pathogens use theendocytic pathway to get into cells e.g.: flu virus Salmonella ?
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- 11. Receptor-Mediated Endocytosis andExocytosis Ligand binds to membrane receptor.Extracellular fluid Intracellular fluid Receptor 1
- 12. Receptor-Mediated Endocytosis andExocytosis 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 andExocytosis 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 andExocytosis 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 andExocytosis 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 andExocytosis 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 andExocytosis 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 andExocytosis 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 andExocytosis 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 Formsspecial 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 assembleinto a cage like structure Fibrous network of pentagons and hexagons Can self-assemble and form empty cages
- 23. Adapter and assemblyproteins 23 Assembly is directed by adapter and assembly proteins Adaptins Responsible for specificity of trafficking
- 24. 24 Dynamin and Vesiclebudding 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 endpointof the endocytosis pathway for many molecules is the lysosome, a highly acidic organelle rich in degradative enzymes.
- 26. Types of endocytoticvesicles 26 Use different coats or no coats Have different sizes Have different mechanisms of forming
- 27. Ligands that enterby receptor mediated endocytosis 27 Nutrients: Cholesterol through LDL receptor Iron with carrier protein transferrin
- 28. Termination of signallingby 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 thatenter by receptor mediated endocytosis 29 Toxins Diphtheria toxin Pseudomonas toxin Cholera toxin Viruses Rous sarcoma virus Vesicular stomatitis virus Adenovirus
- 30. Rates of Clathrinmediated endocytosis 30 Class I LDL and transferrin Constitutive (no ligand necessary) Class II Insulin and EGF Active upon ligand binding
- 31. Rates of Clathrinmediated 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
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- 37. CONCLUSION Receptor-mediated endocytosisis 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 andDale’s Pharmacology H.P.Rang, M.M.Dale, J.M.Ritter, R.J.Flower.2007:6th edition:Pg:24-28. D.M.Brahmankar , Sunil B.Jaiswal. Biopharmaceutics and Pharmacokinetics A Treatise. Published by M.K.Jain.1995:1st 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.2007:3rd 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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