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Regulation of cell-cell interactions by polysialic acid

Yang, Pinfen
http://rave.ohiolink.edu/etdc/view?acc_num=case1057079377

Abstract Details

1993, Doctor of Philosophy, Case Western Reserve University, Neurosciences.
Polysialic acid (PSA), is a long linear homopolymer of sialic acid. In the vertebrate embryo, PSA appears to be exclusively covalently attached a cell surface protein called neural cell adhesion molecule (NCAM). In this context, PSA has been shown to be an important modulator of cell interactions during development, for example in axonal pathfinding and branching, response of axons to loss of synaptic activity and in the migration of muscle cells. The function of PSA has been proposed to influence not only interactions mediated by NCAM itself, but cell-cell interactions in general. In the latter mode, the polymer has been proposed to occupy a significant volume of space at the cell surface, thereby restricting membrane-membrane and/or receptor-receptor contact. Such a model makes specific predictions about the physical nature of PSA, its abundance at the cell surface, and the mechanism by which it regulates cell interactions. This thesis research is specifically designed to test those predictions. The studies described here provide three lines of evidence that the large hydration volume and/or charge repulsion properties of PSA contribute to its function at the cell surface. In the first part, purified NCAM and PSA-expressing tissue culture cells were used to measure the size and density of PSA on the cell surface. The results suggests that a subs tantial fraction of the space between two apposed cell surface membranes can be influenced sterically by the presence of PSA. In addition, specific enzymatic removal of PSA was found to cause a significant reduction in the distance between apposed cell membranes, whereas removal of heparan sulfate and chondroitin sulfate from the cells had no effect. The magnitude of these effects appear to be consistent with a selective alteration of the efficiency of encounter between complementary receptors on apposing cells. In the third line of study, it was demonstrated that the effect of PSA on membrane vesicle aggregation is inversely related to the ionic strength, providing further evidence that the hydration and/or charge repulsion of the anionic polymer underlies its biological activity.
n/a n/a (Advisor)
147 p.
cell-cell interactions; polysialic acid

Recommended Citations

Citations

  • Yang, P. (1993). Regulation of cell-cell interactions by polysialic acid [Doctoral dissertation, Case Western Reserve University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=case1057079377

    APA Style (7th edition)

  • Yang, Pinfen. Regulation of cell-cell interactions by polysialic acid. 1993. Case Western Reserve University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=case1057079377.

    MLA Style (8th edition)

  • Yang, Pinfen. "Regulation of cell-cell interactions by polysialic acid." Doctoral dissertation, Case Western Reserve University, 1993. http://rave.ohiolink.edu/etdc/view?acc_num=case1057079377

    Chicago Manual of Style (17th edition)

case1057079377
413
© 1993, all rights reserved.
This open access ETD is published by Case Western Reserve University School of Graduate Studies and OhioLINK.