Recepter mediated endocytosis by kk ashu

Recepter mediated endocytosis by kk ashu

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  By KAUSHAL KUMAR SAHU AssistantProfessor (Ad Hoc) Department of Biotechnology Govt. Digvijay Autonomous P. G. College Raj-Nandgaon ( C. G. )
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  SYNOPSIS O INTRODUCTION O DEFINITIONOF 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
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  INTRODUCTION  Eukaryotic cellsare 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.
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  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.
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  What types ofligands 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
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  FORMATION OF CLATHRIN-COATEDVESICLES 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.
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  Coated pits invaginateinto 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.
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  O A coatedvesicle that is no longer attached to the plasma membrane. The next step in the process is the release of the clathrin coat. . COATED PITS
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  TRISKELIONS O The geometricconstruction 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.
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  The arrangement oftriskelions and adaptors in the outer clathrin coat.
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  The role ofdynamin 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.
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  The Role ofPhosphoinositides 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.
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  ENDOCYTIC PATHWAY Molecules takeninto a cell by endocytosis are routed through a well-defined endocytic pathway.
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  LDLs and CholesterolMetabolism 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.
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  CONCLUSION O Receptor-mediated endocytosisis 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.
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  REFERENCES O Cell andMolecular Biology- Gerald Karp O Molecular Cell Biology- (Lodish) 5th edition O Alberts- Molecular Biology of cell O INTERNET- www.google.com www.wikipedia.com