PaxB, an orthologue of mammalian paxillin, regulates adhesion, differentiation, and morphogenesis in Dictyostelium discoideum.
Item
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Title
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PaxB, an orthologue of mammalian paxillin, regulates adhesion, differentiation, and morphogenesis in Dictyostelium discoideum.
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Identifier
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AAI3296981
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identifier
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3296981
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Creator
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Duran, Maria-Berenice.
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Contributor
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Adviser: Derrick Brazill
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Date
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2008
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Language
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English
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Publisher
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City University of New York.
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Subject
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Biology, Molecular
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Abstract
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The adhesion of cells to other cells and to the surrounding extracellular matrix is essential for survival, proliferation, differentiation and migration. Focal adhesions, sites where cells are adhered to their substratum, are also important components for tissue formation and wound repair. As in animal cells, such adhesion is critical for the development of the eukaryote Dictyostelium discoideum. In fact, D. discoideum development displays many of the features of animal embryogenesis such as regulated cell-cell adhesion, cell motility and cell morphogenesis. D. discoideum live as individual cells under vegetative conditions, but develop into a multicellular organism under starvation. Cell-cell adhesion is a vital factor for D. disciodeum morphogenesis and is required for multicellular development past the aggregation stage. As in animals, D. discoideum cell adhesion molecules have a mechanical function and may interact with the signal-transduction processes regulating morphogenesis. One regulator protein, PaxB, is an orthologue of mammalian paxillin, a known focal adhesion molecule. Paxillin functions as a docking site on the plasma membrane for signaling and structural proteins, and has been found to play a role in cell-cell cohesion as well as cell-substrate adhesion.;To gain a better understanding of the role and regulation of paxillin, we studied the role of D. disciodeum PaxB in differentiation and development. In particular we describe the effects of PaxB overexpression in adhesion and cell-type differentiation. PaxB overexpressing cells (PaxBOE) exhibit increased cell-cell cohesion in non-nutrient buffer, which is lost when Ca2+ is chelated by EDTA. This suggests adhesion mediated by PaxB is calcium dependent. Interestingly, cells overexpressing paxB are less adhesive to the substratum under equivalent conditions. We show PaxB undergoes serine phosphorylation. In addition, PaxB undergoes adhesion-dependent tyrosine and serine phosphorylation, which is also Ca 2+ dependent. PaxBOE cells can aggregate and form mounds, but subsequent morphogenesis is blocked. This block can be rescued by addition of wild-type cells, indicating a non-cell autonomous role for PaxB. In these chimeras, wild-type cells predominantly localize to the middle section of the spore mass, while PaxBOE cells preferentially are excluded from the spore mass. Taken together, the data suggest calcium dependent cell-substrate adhesion correlates with changes in PaxB tyrosine and serine phosphorylation. The data also imply that proper PaxB protein expression is required for development past the mound stage and for appropriate cell sorting, cell-type differentiation, cell-cell cohesion, and cell-substrate adhesion.
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Type
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dissertation
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Source
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PQT Legacy CUNY.xlsx
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degree
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Ph.D.
