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The role of the Scribble Protein Complex in the regulation of Dendrite Formation

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dc.contributor.advisor Shelly, Maya en_US
dc.contributor.author Sun, Bingru en_US
dc.contributor.other Department of Biological Sciences en_US
dc.date.accessioned 2017-09-20T16:51:32Z
dc.date.available 2017-09-20T16:51:32Z
dc.date.issued 2015-12-01
dc.identifier.uri http://hdl.handle.net/11401/76962 en_US
dc.description 31 pgs en_US
dc.description.abstract During neuronal development, the neuronal cell polarizes to specify the structures of axons and dendrites. This polarized architecture regulates the input/output functions of the neuronal cell. In my thesis, I studied the molecular mechanisms of dendrite formation. My main hypothesis was that dendrite specification results from local elevation of the cGMP signal. Soluble guanylyl cyclase (sGC) is the major enzyme for the synthesis of cGMP in the embryonic brain. I study the molecular mechanism that activates sGC and leads to dendrite specification during neuronal polarization.Scribble is a scaffold protein, part of a polarity complex that establish apical-basal polarity in epithelial cells. In neurons, Scribble has been shown to associate with neuronal nitric oxide synthase (nNOS) that produces the molecule NO. NO activates sGC and can induce cGMP elevation. I hypothesize that dendrite specification is regulated by a polarity protein complex consisting of Scribble, sGC, and nNOS. In my thesis, I found the following: First, I show that Scribble and sGC associate biochemically in the rat embryonic brain. Second, I further characterized the interaction domain between Scribble and sGC and found a protein domain named IMR to be significant. I found that this single domain mutant of Scribble is a dominant negative inhibitor of the function of wild-type Scribble. Last, using shRNA-mediated knockdown of Scribble and sGC in dissociated hippocampal neuron culture, I found severe effects on dendrite development compared to control. Thus, based on my biochemistry studies and functional analysis in cultured neurons, I conclude that the protein complex involving Scribble and sGC regulates dendrite development through the cGMP pathway en_US
dc.description.sponsorship This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree. en_US
dc.format Monograph en_US
dc.format.medium Electronic Resource en_US
dc.language.iso en_US en_US
dc.publisher The Graduate School, Stony Brook University: Stony Brook, NY. en_US
dc.subject.lcsh Biology en_US
dc.title The role of the Scribble Protein Complex in the regulation of Dendrite Formation en_US
dc.type Thesis en_US
dc.mimetype Application/PDF en_US
dc.contributor.committeemember Ge, Shaoyu en_US

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