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Full-Text Articles in Cell Biology

Tissue Retention Of Norrin: A Ligand Required For Retinal Vascularization, Lavan Khandan Jan 2017

Tissue Retention Of Norrin: A Ligand Required For Retinal Vascularization, Lavan Khandan

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

The Norrin ligand is a small (14 kDa) cystine-knot protein, required for the proper vascularization of retinal, cerebellar and inner ear neural tissue. Both inherited human disorders and murine genetic studies implicate Norrin mutations in major ocular and visual defects, including retinal hypovascularization. In this thesis, I describe the property of Norrin enrichment at specific layers in the retina. I address the question of whether proper Norrin distribution in retinal tissue is required for vascularization. To do so, I used ex vivo ligand in-situ staining to interrogate differences amongst vertebrate Norrin orthologues in retinal tissue retention. I then used sequence ...


Elucidating The Ligand-Specific Role Of Tetraspanin12 As An Essential Co-Activator In Norrin/Frizzled4 Signaling And Retinal Vascularization, Maria B. Lai Jan 2017

Elucidating The Ligand-Specific Role Of Tetraspanin12 As An Essential Co-Activator In Norrin/Frizzled4 Signaling And Retinal Vascularization, Maria B. Lai

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Genetic evidence indicates that specific combinations of accessory proteins and ligands mediate vascular Frizzled (FZD) signaling via beta-catenin in different CNS structures. Accessory proteins in FZD receptor complexes are thought to determine ligand-selectivity and signaling amplitude. In the retina, TSPAN12 is an essential co-activator in Norrin/FZD4 signaling to mediate angiogenesis. The genes encoding mediators of Norrin/FZD4 signaling are linked to familial exudative vitreoretinopathy (FEVR), an inherited retinal disease that can lead to blindness. Yet, the molecular function of TSPAN12 and the specific cell type in which TSPAN12 functions in the retina remains poorly understood. Here, I utilized binding ...


Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson Jan 2017

Identification And Characterization Of Regulators Of Glut4 Trafficking, Daniel Richard Gulbranson

Molecular, Cellular, and Developmental Biology Graduate Theses & Dissertations

Cargo proteins moving between organelles are transported by membrane-enclosed vesicles. Identifying the factors regulating vesicle-mediated transport remains a major challenge in mammalian cells. Here, we performed unbiased genome-wide CRISPR-Cas9 genetic screens to systematically dissect insulin-dependent translocation of glucose transporters (GLUTs), a classic vesicle transport pathway crucial to mammalian physiology. These screens identified known regulators of the pathway as well as a large number of unknown regulatory factors that we validated in secondary screens. The identified genes encode established or predicted factors involved in vesicle budding or fusion, cargo sorting, signal transduction, cell motility, and cellular metabolism, as well as proteins ...