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Title: The role of SDCCAG3 in apoptosis and ciliogenesis
Author: Sharma, Shruti
ISNI:       0000 0004 5993 2670
Awarding Body: University of Sheffield
Current Institution: University of Sheffield
Date of Award: 2016
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Serologically defined colon cancer antigen-3 (SDCCAG3) is a coiled-coil domain containing protein that has been implicated in various cellular processes such as endosomal sorting, vesicular trafficking, and cytokinesis. The current study has identified two novel roles of SDCCAG3 i.e. regulation of Fas mediated apoptosis and ciliogenesis. This study demonstrates that SDCCCAG3 is involved in post-endocytic sorting of Fas receptors (a type I transmembrane receptor involved in apoptotic signalling). Depletion of SDCCAG3 by RNA interference led to a delay in transitioning of internalized Fas receptors from early to late endosomes/lysosomes, which resulted in an increased surface population of Fas receptors and consequently increased apoptotic signalling. Further in depth analysis revealed a defect in the intraluminal vesicle sorting of Fas receptors in the absence of SDCCAG3. Dysbindin, a cytosolic protein known to link proteins with the ESCRT machinery, was found to be involved with SDCCAG3 in sorting of Fas receptors for lysosomal degradation. This study also proposes the plausible complex formation between SDCCAG3 and a known negative regulator of Fas receptors, PTPN13, at the early/sorting endosomes. In conclusion, this study identified a novel role of SDCCAG3 in negative regulation of apoptotic signalling. Current research also defines a role of SDCCAG3 in ciliogenesis. Unpublished data from the Erdmann lab suggested a direct interaction between SDCCAG3 and intraflagellar transport protein-88 (IFT88), a central protein involved in ciliogenesis and ciliary trafficking (Yu, unpublished data). Similar to IFT88, SDCCAG3 was also found to localize at the basal body, regulate cilia formation and ciliary length in IMCD3 cells in this study. Additionally, depletion of SDCCAG3 affected localization of a transmembrane protein called Polycystin-2 and not Rab8 to cilia. Defects in Polycystin-2 trafficking to cilia have been linked to polycystic kidney disorder in numerous studies. Thus, this study establishes SDCCAG3 as a novel ciliary protein involved in ciliogenesis and trafficking.
Supervisor: Kai, Erdmann Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available