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      Endocytosis unplugged: multiple ways to enter the cell

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          Abstract

          Endocytosis occurs at the cell surface and involves internalization of the plasma membrane (PM) along with its constituent membrane proteins and lipids. Endocytosis is involved in sampling of the extracellular milieu and also serves to regulate various processes initiated at the cell surface. These include nutrient uptake, signaling from cell-surface receptors, and many other processes essential for cell and tissue functioning in metazoans. It is also central to the maintenance of PM lipid and protein homeostasis. There are multiple means of internalization that operate concurrently, at the cell surface. With advancement in high-resolution visualization techniques, it is now possible to track multiple endocytic cargo at the same time, revealing a remarkable diversity of endocytic processes in a single cell. A combination of live cell imaging and efficient genetic manipulations has also aided in understanding the functional hierarchy of molecular players in these mechanisms of internalization. Here we provide an account of various endocytic routes, their mechanisms of operation and occurrence across phyla.

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          Regulated portals of entry into the cell.

          The plasma membrane is the interface between cells and their harsh environment. Uptake of nutrients and all communication among cells and between cells and their environment occurs through this interface. 'Endocytosis' encompasses several diverse mechanisms by which cells internalize macromolecules and particles into transport vesicles derived from the plasma membrane. It controls entry into the cell and has a crucial role in development, the immune response, neurotransmission, intercellular communication, signal transduction, and cellular and organismal homeostasis. As the complexity of molecular interactions governing endocytosis are revealed, it has become increasingly clear that it is tightly coordinated and coupled with overall cell physiology and thus, must be viewed in a broader context than simple vesicular trafficking.
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            Caveolin, a protein component of caveolae membrane coats.

            Caveolae have been implicated in the transcytosis of macromolecules across endothelial cells and in the receptor-mediated uptake of 5-methyltetrahydrofolate. Structural studies indicate that caveolae are decorated on their cytoplasmic surface by a unique array of filaments or strands that form striated coatings. To understand how these nonclathrin-coated pits function, we performed structural analysis of the striated coat and searched for the molecular component(s) of the coat material. The coat cannot be removed by washing with high salt; however, exposure of membranes to cholesterol-binding drugs caused invaginated caveolae to flatten and the striated coat to disassemble. Antibodies directed against a 22 kd substrate for v-src tyrosine kinase in virus-transformed chick embryo fibroblasts decorated the filaments, suggesting that this molecule is a component of the coat. We have named the molecule caveolin. Caveolae represent a third type of coated membrane specialization that is involved in molecular transport.
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              Virus Entry: Open Sesame

              Detailed information about the replication cycle of viruses and their interactions with host organisms is required to develop strategies to stop them. Cell biology studies, live-cell imaging, and systems biology have started to illuminate the multiple and subtly different pathways that animal viruses use to enter host cells. These insights are revolutionizing our understanding of endocytosis and the movement of vesicles within cells. In addition, such insights reveal new targets for attacking viruses before they can usurp the host-cell machinery for replication.
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                Author and article information

                Contributors
                +91-80-2366-6420 , +91-80-2363-6662 , mayor@ncbs.res.in
                Journal
                Cell Res
                Cell Res
                Cell Research
                Nature Publishing Group UK (London )
                1001-0602
                1748-7838
                2 February 2010
                March 2010
                : 20
                : 3
                : 256-275
                Affiliations
                [1 ]GRID grid.22401.35, ISNI 0000 0004 0502 9283, National Centre for Biological Science (TIFR), ; Bellary Road, Bangalore, 560 065 Karnataka India
                [2 ]GRID grid.137628.9, ISNI 0000 0004 1936 8753, Present Address: current address: Molecular Pathogenesis, Marty and Helen Kimmel Center for Biology and Medicine of the Skirball Institute for Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, ; ,
                Article
                BFcr201019
                10.1038/cr.2010.19
                7091825
                20125123
                cf7922b7-8ad0-44de-8724-34bca988952f
                © Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences 2010

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

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                © IBCB, SIBS, CAS 2010

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