受容体インターナリゼーション

WordNet

a cellular structure that is postulated to exist in order to mediate between a chemical agent that acts on nervous tissue and the physiological response
learning (of values or attitudes etc.) that is incorporated within yourself (同)internalisation, incorporation

PrepTutorEJDIC

=sense organ / 受信装置

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/06/16 19:36:02」(JST)

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Mechanism of clathrin-dependent endocytosis.

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

Process

After the binding of a ligand to plasma membrane-spanning receptors, a signal is sent through the membrane, leading to membrane coating, and formation of a membrane invagination. The receptor and its ligand are then opsonized in clathrin-coated vesicles. Once opsonized, the clathrin-coated vesicle uncoats (a pre-requisite for the vesicle to fuse with other membranes) and individual vesicles fuse to form the early endosome. Since the receptor is internalized with the ligand, the system is saturable and uptake will decline until receptors are recycled to the surface.

Function

The function of receptor-mediated endocytosis is diverse. It is widely used for the specific uptake of certain substances required by the cell (examples include LDL via the LDL receptor or iron via transferrin). The role of receptor-mediated endocytosis is also well recognized in the downregulation of transmembrane signal transduction. The activated receptor becomes internalised and is transported to late endosomes and lysosomes for degradation. However, receptor-mediated endocytosis is also actively implicated in transducing signals from the cell periphery to the nucleus. This became apparent when it was found that the association and formation of specific signaling complexes is required for the effective signaling of hormones (e.g. EGF). Additionally it has been proposed that the directed transport of active signaling complexes to the nucleus might be required to enable signaling as random diffusion is too slow^[1] and mechanisms permanently downregulating incoming signals are strong enough to shutdown signaling completely without additional signals transducing mechanisms.^[2]

Experiments

Using fluorescent dyes to stain the plasma membrane, it is possible to follow the internalization of plasma membrane fragments by microscopy.

Since the process is non-specific, the ligand can be a carrier for larger molecules. If the target cell has a known specific pinocytotic receptor, drugs can be attached and will be internalized.

Specific Properties

induction within minutes of exposure to excess ligand.
the formation of these vesicles is sensitive to inhibition by wortmannin^{[citation needed]}
the initiation of vesicle formation can be delayed/inhibited by temperature variations

References

^ Howe, Charles L. (2005). "Modeling the Signaling Endosome Hypothesis: Why a Drive to the Nucleus Is Better Than a (Random) Walk". Theor. Biol. Med. Mod 2 (1): 43. doi:10.1186/1742-4682-2-43. PMC 1276819. PMID 16236165. 2:43.
^ Kholodenko, Boris N. (2003). "Four-Dimensional Organisation of Protein Kinase Signaling Cascades: the Roles of Diffusion, Endocytosis and Molecular Motors". J. Exp. Biol 206 (Pt 12): 2073–82. doi:10.1242/jeb.00298. PMID 12756289. 206, 2073-2082.

External links

CytoChemistry.net- A lecture on RME with some nice pictures

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UpToDate Contents

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English Journal

Folate-modified poly(2-ethyl-2-oxazoline) as hydrophilic corona in polymeric micelles for enhanced intracellular doxorubicin delivery.

Qiu LY, Yan L, Zhang L, Jin YM, Zhao QH.SourceCollege of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China.
International journal of pharmaceutics.Int J Pharm.2013 Nov 18;456(2):315-24. doi: 10.1016/j.ijpharm.2013.08.071. Epub 2013 Sep 7.
The transmembrane transport of drug loaded micelles to intracellular compartment is quite crucial for efficient drug delivery. In the current study, we investigated the cellular internalization and anticancer activity of doxorubicin loaded micelles with folate modified stealthy PEOz corona. Folate-d
PMID 24016742

Novel biotinylated chitosan-graft-polyethyleneimine copolymer as a targeted non-viral vector for anti-EGF receptor siRNA delivery in cancer cells.

Darvishi MH, Nomani A, Amini M, Shokrgozar MA, Dinarvand R.SourceDepartment of Medical Nanotechnology, School of Advanced Technologies in Medicine, Tehran University of Medical Sciences, Tehran, Iran; Nanotechnology Research Centre, Tehran University of Medical Sciences, Tehran, Iran.
International journal of pharmaceutics.Int J Pharm.2013 Nov 18;456(2):408-16. doi: 10.1016/j.ijpharm.2013.08.069. Epub 2013 Sep 3.
The major impediments to develop an efficient non-viral siRNA-mediated gene silencing method, as a therapeutic approach, are the low cellular uptake and intracellular delivery and release of non-viral vectors. To overcome these problems, designing a proper vector with high transfection efficiency is
PMID 24012865

Bioimaging and pulmonary applications of self-assembled Flt1 peptide-hyaluronic acid conjugate nanoparticles.

Kim H, Park HT, Tae YM, Kong WH, Sung DK, Hwang BW, Kim KS, Kim YK, Hahn SK.SourceDepartment of Materials Science and Engineering, Pohang University of Science and Technology (POSTECH), San 31, Hyoja-dong, Nam-gu, Pohang, Kyungbuk 790-784, Republic of Korea.
Biomaterials.Biomaterials.2013 Nov;34(33):8478-90. doi: 10.1016/j.biomaterials.2013.07.062. Epub 2013 Aug 6.
Despite wide exploitation of corticosteroid drugs for the treatment of asthma, the poor therapeutic effect on a neutrophilic subtype of asthma prohibits the full recovery of asthma patients. In this work, dexamethasone (Dexa) was loaded in Flt1 peptide-hyaluronic acid (HA) conjugate nanoparticles to
PMID 23932502

Japanese Journal

Insulin Induces Internalization of the Plasma Membrane 5-Hydroxytryptamine2A (5-HT2A) Receptor in the Isolated Human Endothelium-Denuded Saphenous Vein via the Phosphatidylinositol 3-Kinase Pathway

Kanai Tasuku,Kuwabara Masachika,Tanaka-Totoribe Naoko [他]
Journal of pharmacological sciences 118(2), 178-185, 2012-02
NAID 40019161559

Fluorescence ratiometric detection of ligand-induced receptor internalization using extracellular coiled-coil tag-probe labeling.

Yano Yoshiaki,Matsuzaki Katsumi
FEBS letters 585(14), 2385-2388, 2011-07-21
… We report a new method for the detection of ligand-induced receptor internalization by fluorescence ratiometric imaging of pH in endosomes in combination with a recently developed posttranslational labeling system based on the formation of a heterodimeric coiled-coil structure. … The N-terminus of the β2-adrenergic receptor expressed on the cell surface was doubly labeled with pH-sensitive fluorescein and pH-insensitive tetramethylrhodamine. …
NAID 80021902638

Related Pictures

★リンクテーブル★

リンク元	「受容体インターナリゼーション」
拡張検索	「receptor internalization and degradation」
関連記事	「internalization」