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Characterization of Protocadherin-21 in photoreceptor disk synthesis

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dc.contributor.author Lee Ling, Yang
dc.date.accessioned 2012-11-19T17:01:52Z
dc.date.available 2013-05-31
dc.date.copyright 2012 en_US
dc.date.issued 2012-11-19
dc.identifier.uri http://hdl.handle.net/2429/43594
dc.description.abstract Protocadherin-21 (pcdh-21) is a transmembrane protein concentrated at nascent disks in mouse photoreceptors and thought to regulate disk synthesis. PCDH-21 mutations are associated with retinal degenerative diseases. Pcdh-21 undergoes proteolytic cleavage that may be essential for disk synthesis. In mice, Pcdh-21 interacts with prominin-1 (prom-1) and their interaction may be required for their localization and function in disk synthesis. To compare pcdh-21 localization across species, we performed immunofluorescence microscopy using an antibody raised against the N-terminus of X.laevis pcdh-21 (xpcdh-21). In rods and cones of all species, pcdh-21 was localized to nascent disks at the base of the outer segment, suggesting a conserved role in disk assembly. However, in contrast with the idea that pcdh-21 localizes only to the basal outer segment, pcdh-21 was localized to other outer segment regions, and this localization was different across cell types and species, suggesting that pcdh-21 has cell type- and species- specific structural roles. Pcdh-21 was restricted to open disk rims in X.laevis cones. Prom-1, an interacting partner of pcdh-21 in mice, shows identical labeling at the open disk rims. Pcdh-21 and prom-1 may therefore interact to maintain open disk structure. Immunoblots showed that proteolytic cleavage of pcdh-21 may be unique to mice. In X.laevis rods, pcdh-21 labeling in the nascent disks did not vary with disk synthesis rate. We attempted to inhibit pcdh-21 function using a dominant negative approach. Full length pcdh-21 (FL) and deletion constructs consists of mouse (mpcdh-21) and xpcdh-21 were overexpressed in X.laevis rods. Retinal degeneration and disk defects were only observed in retinas overexpressing mpcdh-21 FL. Mpcdh-21 FL was retained in the ER, caused abnormal ER structure, and was not cleaved in X. laevis retinas. Xpcdh-21 variants were correctly localized and did not cause retinal degeneration. This study illustrated that pcdh-21 localization, processing and properties may not be conserved across species. Differences in pcdh-21 localization may reflect differences in disk synthesis mechanisms or disk ultrastructure. However, the conserved association of pcdh-21 and prom-1 with open disk rims and nascent disks suggests that they may form a complex involved in regulating disk synthesis and/ or in maintaining disk structure. en_US
dc.language.iso eng en_US
dc.publisher University of British Columbia en
dc.title Characterization of Protocadherin-21 in photoreceptor disk synthesis en_US
dc.type Electronic Thesis or Dissertation en
dc.degree.name Master of Science - MSc en_US
dc.degree.discipline Cell and Developmental Biology en_US
dc.degree.grantor University of British Columbia en
dc.date.graduation 2013-05 en_US
dc.degree.campus UBCV en_US
dc.description.scholarlevel Graduate en


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