Clathrin-mediated endocytosis

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Mechanism of clathrin-mediated endocytosis

The clathrin-mediated endocytosis is the uptake of molecules in eukaryotic cells via clathrin -coated vesicles . It is one of the four mechanisms of endocytosis and the main one. This form also counts as receptor-mediated endocytosis.

properties

In clathrin-mediated endocytosis, an area of ​​the cell membrane becomes vesicles within the cell through invagination and constriction. This mechanism is the main mechanism of endocytosis in most cells. Over 50 proteins are involved in this. After a ligand has bound to its receptor , the invagination is promoted by the protein clathrin on the inside of the cell membrane. Clathrin is located in certain areas of the cell membrane to clathrin-coated pits ( clathrinbeschichtete wells ). After constriction, the clathrin-coated vesicles ( clathrin-coated vesicles ) have a diameter of approx. 100 nm. The constriction takes place through the formation of a ring of dynamins . After binding to a receptor on the cell membrane, various proteins are transported into the cell via clathrin vesicles, e.g. B. LDL , transferrin , growth factors and antibodies . The corresponding receptors are the LDL receptor , the transferrin receptor , the EGF receptor and the Fc receptor .

Cells regulate the receptor density on the cell membrane and thus the signal intensity of the receptors when activated by endocytosis of receptors, which means that they are available for a longer or shorter period of time for the binding of a ligand . The clathrin-mediated endocytosis can interrupt signal transduction at the cell membrane.

Some receptors are endocytosed with, others without, bound ligands. In the case of receptors with bound ligands, signal transduction of the receptor also takes place from the vesicle in some cases . After the receptor has bound to an adapter and sorting protein such as numb or disabled in the well, other proteins such as AP-2 and EHD proteins are bound. At the beginning of endocytosis, the secondary messenger substance PI (4,5) P 2 is formed as the depression builds up, while it is degraded in the further course of the ripening of the depression and PI (3,4) P 2 is formed instead . The transport of vesicles occurs along the actin - cytoskeleton .

Clathrin-mediated endocytosis can be divided into eight phases: determination of the location, recruitment of clathrin and adapter proteins, indentation of the cell membrane, depression, beginning of inclusion by inward movement of the depression, constriction of the vesicle, movement of the vesicle along the cytoskeleton, recycling of the proteins in the vesicle and fusion with an endosome.

Some viruses use clathrin-mediated endocytosis to get into cells, such as: B. the hemagglutinin of the influenza virus , the VSV-G of the vesicular stomatitis virus and the adenovirus , while other viruses penetrate the cell membrane directly.

Individual evidence

  1. ↑ V. Bitsikas, IR Corrêa, BJ Nichols: clathrin-independent pathways do not contribute to Significantly endocytic flux. In: eLife. Volume 3, 2014, p. E03970, doi : 10.7554 / eLife.03970 , PMID 25232658 , PMC 4185422 (free full text).
  2. ↑ T. Kirchhausen, D. Owen, SC Harrison: Molecular Structure, Function, and Dynamics of Clathrin-Mediated Membrane Traffic. In: Cold Spring Harbor Perspectives in Biology. 6, 2014, p. A016725, doi : 10.1101 / cshperspect.a016725 .
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  4. ↑ CJ Merrifield, M. Kaksonen: Endocytic accessory factors and regulation of clathrin-mediated endocytosis. In: Cold Spring Harbor perspectives in biology. Volume 6, Number 11, November 2014, p. A016733, doi : 10.1101 / cshperspect.a016733 , PMID 25280766 .
  5. ↑ Alexander Sorkin, Manojkumar A. Puthenveedu: Yosef Yarden (ed.): Clathrin-Mediated Endocytosis ( en ). Springer New York, January 1, 2013, ISBN 978-1-4614-6527-0 , pp. 1–31, doi : 10.1007 / 978-1-4614-6528-7_1 .
  6. ↑ AC Sundborger, JE Hinshaw: Regulating dynamin dynamics during endocytosis. In: F1000prime reports. Volume 6, 2014, p. 85, doi : 10.12703 / P6-85 , PMID 25374663 , PMC 4191240 (free full text).
  7. ↑ PP Di Fiore, M. von Zastrow: Endocytosis, signaling, and beyond. In: Cold Spring Harbor perspectives in biology. Volume 6, number 8, August 2014, p., Doi : 10.1101 / cshperspect.a016865 , PMID 25085911 .
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  10. ↑ Boris N. Kholodenko: Four-Dimensional Organization of Protein Kinase Signaling Cascades: the Roles of Diffusion, Endocytosis and Molecular Motors . In: J. Exp. Biol. . 206, No. Pt 12, 2003, pp. 2073-82. 206, 2073-2082. doi : 10.1242 / jeb.00298 . PMID 12756289 .
  11. ^ A b C. C. Yap, B. Winckler: Adapting for endocytosis: roles for endocytic sorting adapters in directing neural development. In: Frontiers in cellular neuroscience. Volume 9, 2015, p. 119, doi : 10.3389 / fncel.2015.00119 , PMID 25904845 , PMC 4389405 (free full text) (review).
  12. ↑ Y. Posor, M. Eichhorn-Grunig, V. Hauke: phosphoinositides in endocytosis. In: Biochimica et Biophysica Acta . Volume 1851, number 6, June 2015, pp. 794-804, doi : 10.1016 / j.bbalip.2014.09.014 , PMID 25264171 .
  13. ↑ ES Kornilova: Receptor-mediated endocytosis and cytoskeleton. In: Biochemistry. Biokhimii? A ?. Volume 79, Number 9, September 2014, pp. 865-878, doi : 10.1134 / S0006297914090041 , PMID 25385015 .
  14. ↑ S. Boulant, M. Stanifer, PY Lozach: Dynamics of virus-receptor interactions in virus binding, signaling, and endocytosis. In: Viruses. Volume 7, number 6, June 2015, pp. 2794-2815, doi : 10.3390 / v7062747 , PMID 26043381 , PMC 4488714 (free full text).
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