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Publicly Accessible Penn Dissertations

Wnt

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Full-Text Articles in Cell Biology

Palmitoylation And Polarity: Regulation Of Asymmetric Partitioning Of Notch And Wnt Signaling By Reversible Lipid Modification In Dividing Cells, Ewa Stypulkowski Jan 2018

Palmitoylation And Polarity: Regulation Of Asymmetric Partitioning Of Notch And Wnt Signaling By Reversible Lipid Modification In Dividing Cells, Ewa Stypulkowski

Publicly Accessible Penn Dissertations

Protein palmitoylation is a reversible lipid modification that regulates protein-membrane interaction, activity, trafficking, and stability in a spatio-temporal manner similar to phosphorylation and ubiquitination. Asymmetric cell division results in two distinctly fated daughter cells, by unequally partitioning proteins known as cell fate determinants. I have characterized a mechanism for protein palmitoylation to asymmetrically partition cell fate determinants, e.g. Numb and β-catenin, through the activity of the depalmitoylating enzyme APT1. Using point mutations, I have found specific palmitoylated residues on Numb are required for its asymmetric localization in dividing cells. By live-cell imaging, I have also identified a reciprocal interaction ...


Investigating The In Vivo Role Of Wnt Acylation, Kelsey Foss Speer Jan 2017

Investigating The In Vivo Role Of Wnt Acylation, Kelsey Foss Speer

Publicly Accessible Penn Dissertations

Wnts are a family of morphogens that play diverse roles in embryonic patterning, the maintenance of adult stem cells, and the evolution of cancers. Mammalian genomes contain 19 unique Wnt proteins which undergo post-translational acylation at a highly-conserved serine residue. All Wnts bind to the Frizzled (Fz) family of seven-pass transmembrane receptor at an extracellular cysteine-rich domain (CRD). Recent crystallographic evidence suggests that interaction between Wnt and CRD is dependent upon the direct binding of an acyl group on the Wnt to a hydrophobic groove on the CRD. As all vertebrate Wnts are acylated at a conserved site, it is ...


Epithelial Cell Shape Changes During Lung Branching Morphogenesis: The Role Of Wnt/Fzd2 Signaling In Directing New Branch Formation, Rachel S. Kadzik Jan 2014

Epithelial Cell Shape Changes During Lung Branching Morphogenesis: The Role Of Wnt/Fzd2 Signaling In Directing New Branch Formation, Rachel S. Kadzik

Publicly Accessible Penn Dissertations

Formation of the intricately branched mammalian lung requires precise coordination between the epithelium and mesenchyme over the course of development. This coordination is mediated by molecular signaling between the two tissue compartments. How these signaling pathways coordinate changes in cellular and tissue morphology to give rise to the highly ramified branched network of the lung is not well understood. In this work, I show that signaling through Frizzled 2 (Fzd2) is required for promoting changes in epithelial cell shape that lead to tissue-level changes needed for branching morphogenesis in the lung. Through analysis of both fixed lungs and live imaging ...