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
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. 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

20. 20

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:

35. 35

36. 36

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.
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38. REFERENCES
 Rang and Dale’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
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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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