INTRODUCTION DEFINITION OF RECEPTOR MEDIATED ENDOCYTOSIS WHAT TYPE OF LIGANDS ENTER BY RME? FORMATION OF CLATHRIN-COATED VESICLES TRISKELIONS ROLE OF DYNAMIN IN THE FORMATION OF CLATHRIN-COATED VESICLES ROLE OF PHOSPHOLIPIDS IN THE FORMATION OF COATED VESICLES ENDOCYTIC PATHWAY LDLs AND CHOLESTROL METABOLISM CONCLUSION REFERENCES

1. By
KAUSHAL KUMAR SAHU
Assistant Professor (Ad Hoc)
Department of Biotechnology
Govt. Digvijay Autonomous P. G. College
Raj-Nandgaon ( C. G. )

2. SYNOPSIS
O INTRODUCTION
O DEFINITION OF RECEPTOR MEDIATED
ENDOCYTOSIS
O WHAT TYPE OF LIGANDS ENTER BY RME?
O FORMATION OF CLATHRIN-COATED
VESICLES
O TRISKELIONS
O ROLE OF DYNAMIN IN THE FORMATION
OF CLATHRIN-COATED VESICLES
O ROLE OF PHOSPHOLIPIDS IN THE
FORMATION OF COATED VESICLES
O ENDOCYTIC PATHWAY
O LDLs AND CHOLESTROL METABOLISM
O CONCLUSION
O REFERENCES

3. INTRODUCTION
 Eukaryotic cells are able to take up macromolecules and
particles from the surrounding medium by a process called
endocytosis.
 In endocytosis the material to be internalized is surrounded by
an area of plasma membrane, which then buds off inside the
cell to form a vesicle containing the ingested material.
 The term "endocytosis" was coined by Christian deDuve in
1963.
 Endocytosis can be divided broadly into two categories: bulk-
phase endocytosis and receptor-mediated endocytosis.
 Bulk-phase endocytosis (also known as pinocytosis) is the non-
specific uptake of extracellular fluids.
 Receptor-mediated endocytosis, in contrast, brings about the
uptake of specific extracellular macromolecules (ligands)
following their binding to receptors on the external surface of
the plasma membrane.

4. DEFINITION
Receptor-mediated endocytosis (RME), also called
clathrin dependent endocytosis, is a process by which
cells internalize molecules (endocytosis) by the inward
budding of plasma membrane vesicles containing proteins
with receptor sites specific to the molecules being
internalized.

5. What types of ligands enter by receptor
mediated endocytosis?
O Toxins and lectins
Diptheria Toxin
Pseudomonas toxin
Cholera toxin
Ricin
Concanavalin A
O Viruses
Rous sarcoma virus
Semliki forest virus
Vesicular stomatitis virus
Adenovirus
O Serum transport proteins and
antibodies
Low density lipoprotein
Transcobalamin
Yolk proteins
IgE
Polymeric IgA
Maternal IgG
IgG, via Fc receptors
O Hormones and Growth
Factors
Insulin
Epidermal Growth Factor
Growth Hormone
Thyroid stimulating hormone
Nerve Growth Factor
Calcitonin
Glucagon
Prolactin
Luteinizing Hormone
Thyroid hormone

6. FORMATION OF CLATHRIN-COATED VESICLES
O Receptor mediated endocytosis depends on the interaction of the
molecule with a specific binding protein in the cell membrane called a
receptor.
O Substances that enter a cell by means of RME become bound to
receptors that collect in specialized domains of the plasma
membrane, known as coated pits. Receptors are concentrated in
coated pits at 10–20 times their level in the remainder of the plasma
membrane. Coated pits are recognized in electron micrographs as
sites where the surface is indented and the plasma membrane is
covered on its cytoplasmic face by a bristly, electron-dense coat
containing clathrin.

7. Coated pits invaginate into the cytoplasm.
The plasma membrane is about to pinch off as a vesicle containing the
yolk protein on its luminal (previously extracellular) surface and clathrin
on its cytosolic surface.

8. O A coated vesicle that is no longer attached to the plasma membrane.
The next step in the process is the release of the clathrin coat. .
COATED
PITS

9. TRISKELIONS
O The geometric construction of the coat is derived from the structure
of its clathrin building blocks. Each clathrin molecule consists of
three heavy chains and three light chain. The inner portion of each
heavy chain is linked to a smaller light chain. All joined together at
the center to form a three-legged assembly called a triskelion.

10. The arrangement of triskelions and adaptors
in the outer clathrin coat.

11. The role of dynamin in the formation of clathrin-
coated vesicles.
A “real” coated vesicle, may contain upwards of two dozen different
accessory proteins that form a dynamic network of interacting
molecules. These proteins have poorly understood roles in cargo
recruitment, coat assembly, membrane curvature and invagination,
interaction with cytoskeletal components, vesicle release, and
membrane uncoating. The best studied of these accessory proteins
is dynamin.

12. The Role of Phosphoinositides in the Formation of
Coated Vesicles
O The phospholipids of the vesicle membrane also
play an important role.
O Phosphate groups can be added to different
positions of the sugar ring of the phospholipid
phosphatidylinositol (PI), converting them into
phosphoinositides.
O The phosphorylated rings of these
phosphoinositides reside at the surface of the
membrane where they can be recognized and
bound by particular protein.
O The inner leaflet of the plasma membrane, for
example, tends to contain elevated levels of
PI(4,5)P2, which plays an important role in
recruiting proteins involved in clathrin-mediated
endocytosis, such as dynamin and AP2.

13. ENDOCYTIC PATHWAY
Molecules taken into a cell by
endocytosis are routed through
a well-defined endocytic
pathway.

14. LDLs and Cholesterol Metabolism
Among many examples of receptor-mediated endocytosis, the
first studied and best understood is one that provides animal
cells with exogenous cholesterol. Animal cells use cholesterol as
an essential part of their plasma membranes and as a precursor
to steroid hormones. Cholesterol is a hydrophobic molecule that
is transported in the blood as part of huge lipoprotein complexes,
such as the low-density lipoprotein (LDL).
Each LDL particle contains a
central core of about 1500
cholesterol molecules esterified
to long-chain fatty acids.
The core is surrounded by a
single layer of phospholipids that
contains a single copy of a large
protein, called apolipoprotein B-
100, which binds specifically to
LDL receptors on the surfaces of
cells.

15. CONCLUSION
O Receptor-mediated endocytosis is a process by which cells
internalize molecules by the inward budding of plasma
membrane vesicles containing proteins with receptor sites
specific to the molecules being internalized.
O This is highly specific process, the cell takes in only certain
molecules, the specificities of which is determined by receptors
on the cell’s plasma membrane.
O RME is an important mechanism which the body uses to
remove cholesterol from the bloodstream.
O Mammalian cells use receptor-mediated endocytosis to take in
a wide variety of substances like LDL particles, insulin and
most other protein hormones.
O Many of the immune system’s functions are dependent on
receptor-mediated endocytosis.

16. REFERENCES
O Cell and Molecular Biology- Gerald Karp
O Molecular Cell Biology- (Lodish) 5th edition
O Alberts- Molecular Biology of cell
O INTERNET-
www.google.com
www.wikipedia.com