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Release and transport of the secreted signal encoded by wingless

Ricardo, Sara Franco; (2004) Release and transport of the secreted signal encoded by wingless. Doctoral thesis (Ph.D), UCL (University College London). Green open access

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One of the questions of outstanding interest is how a secreted protein such as Wingless is able to travel a distance in order to pattern the tissue away from its source. The Wingless protein of Drosophila (Wg) is a member of the Wnt family of secreted glycoproteins. In the embryonic epidermis it is expressed in one row of cells per segment and acts asymmetrically from the source, while in imaginal discs the spread of Wingless is symmetrical and over a greater distance. The mechanism of Wingless transport is still poorly understood although it has been postulated that Heparan Sulfate Proteoglycans could be involved. HSPGs are abundant at the cell surface and consist of a protein core to which sulfated sugar chains are attached. It has been suggested that Wingless binds to these sugar chains, on secreting or receiving cells. I found that Wingless is mostly retained at the cell surface of secreting cells while very little is observable at the surface of receiving cells. HSPGs are responsible for this retention since when no functional proteoglycans are present. Wingless no longer accumulates at the surface of secreting cells. Interestingly, much Wingless is also lost from the secretory pathway in the absence of mature proteoglycans, suggesting a role for the HSPGs in secreting cells. Although much Wingless remains associated with expressing cells, the signal must be released since it acts at a distance. The mechanism and form by which Wingless is released from secreting cells is not known so I set out to investigate this process and also to ask how it is influenced by HSPGs. Using insect cell lines, I found Wingless to be released to the supernatant of expressing cells in an insoluble and a soluble form. Preliminary characterization of the insoluble form suggests that is membrane bound.

Type: Thesis (Doctoral)
Qualification: Ph.D
Title: Release and transport of the secreted signal encoded by wingless
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Protein transport
URI: https://discovery.ucl.ac.uk/id/eprint/10102711
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